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Mean Arterial Pressure (mean + arterial_pressure)
Selected AbstractsErectile Function in Two-Kidney, One-Clip Hypertensive Rats is Maintained by a Potential Increase in Nitric Oxide ProductionTHE JOURNAL OF SEXUAL MEDICINE, Issue S3 2009A. Elizabeth Linder PhD ABSTRACT Introduction., Hypertension is closely associated with erectile dysfunction (ED) as it has been observed in many experimental models of hypertension. Additionally, epidemiological studies show that approximately a third of hypertensive patients have ED. Aim., To test the hypothesis that the two-kidney, one-clip (2K-1C) rat model of hypertension displays normal erectile function due to increased nitric oxide (NO) production in the penis. Methods., Ganglionic-induced increase in intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was used as an index of erectile function in 2K-1C and in normotensive sham-operated (SHAM) anesthetized rats. Cavernosal strips from hypertensive and normotensive rats were used for isometric tension measurement. The contraction induced by alpha-adrenergic agonist phenylephrine and the relaxation induced by the NO donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the NO synthase inhibitor N, -nitro-L-arginine (L-NNA). Results., Changes in ICP/MAP induced by ganglionic stimulation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were similar in cavernosal strips from both groups. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM. Conclusions., These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is maintained in spite of the increased Rho-kinase activity by increased NO signaling. Linder AE, Dorrance AM, Mills TM, Webb RC, and Leite R. Erectile function in two-kidney, one-clip hypertensive rats is maintained by a potential increase in nitric oxide production. J Sex Med 2009;6(suppl 3):279,285. [source] Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafilBJU INTERNATIONAL, Issue 1 2010Serap Gur Study Type , Aetiology (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of N(G)-nitro- l -arginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODS Thirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTS The erectile response was diminished in the HT group. Nitrergic and endothelium-dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAME-treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONS Sildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT. [source] In Vitro and In Vivo Relaxation of Corpus Cavernosum Smooth Muscle by the Selective Myosin II Inhibitor, BlebbistatinTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2009Xin-hua Zhang MD ABSTRACT Introduction., Blebbistatin (BLEB) is a small cell permeable molecule originally reported as a selective inhibitor of myosin II isoforms expressed by striated muscle and non-muscle cells (IC50 = 0.5,5 µM) with poor inhibition of turkey gizzard smooth muscle (SM) myosin II (IC50,80 µM). However, recently it was found that BLEB can potently inhibit mammalian arterial SM (IC50,5 µM). Aim., To investigate the effect of BLEB on corpus cavernosum SM (CCSM) tone and erectile function (EF). Methods., CC tissue obtained from penile implant patients along with CC, aorta and bladder from adult male rats were used for BLEB organ bath studies. Intracavernosal BLEB was administered to rats and EF was assessed via intracavernous pressure (ICP). Main Outcome Measures., Effects of BLEB on agonist-induced CCSM, aorta and bladder contraction in vitro and ICP in vivo. Results., BLEB completely relaxed human CCSM pre-contracted with phenylephrine (PE) in a dose-dependent manner decreasing tension by 76.5% at 10 µM. BLEB pre-incubation attenuated PE-induced contraction of human CC by ,85%. Human CC strips pre-contracted with endothelin-1 or KCl were almost completely relaxed by BLEB. Rat CCSM pre-contracted with PE showed BLEB relaxation comparable to human CCSM. BLEB inhibition was similar for rat aorta but slower for bladder. Both maximal ICP and ICP/mean arterial pressure were dose-dependently increased by BLEB intracavernous injections with full erection at 1 micromole. Conclusion., Our novel data reveals that BLEB nearly completely relaxes rat and human CCSM pre-contracted with a variety of potent agonists and exhibits tissue selectivity. Coupled with our in vivo data in which nanomole doses of BLEB significantly increase ICP, our data substantiates an important role for the SM contractile apparatus in the molecular mechanism for EF and suggests the possibility of BLEB binding at myosin II as a therapeutic treatment for ED by targeting SM contractile pathways. Zhang X, Aydin M, Kuppam D, Melman A, and DiSanto ME. In vitro and in vivo relaxation of corpus cavernosum smooth muscle by the selective myosin II inhibitor, blebbistatin. J Sex Med 2009;6:2661,2671. [source] Improvement of Outcomes after Coronary Artery Bypass II: A Randomized Trial Comparing Intraoperative High Versus Customized Mean Arterial PressureJOURNAL OF CARDIAC SURGERY, Issue 6 2007Mary E. Charlson M.D. Methods: Patients scheduled to undergo primary elective CABG were eligible. In one group, mean arterial pressure target during CPB was 80 mmHg ("high" MAP group); in the other group, MAP target was determined by patients' pre-bypass MAP ("custom" MAP group). The principal outcomes were mortality, major neurologic or cardiac complications, cognitive complications or deterioration in functional status. Results: Of 412 enrolled patients, 36% were women, with overall mean age of 64.7 ± 12.3 years. Duration of bypass was identical for the two randomization groups. Overall complication rates were similar: 16.5% of the high group and 14.6% of the custom group experienced one or more neurologic, cardiac or cognitive complications. When only cardiac and neurologic morbidity and mortality were considered, the rates were 11.7% and 12.6%, in the high and custom groups, respectively. The aggregate outcome rate, including functional deterioration, was 31.6% in the high group and 29.6% in the custom group. Conclusions: There were no statistically significant differences between the high MAP group and the custom MAP group for the combined outcome of mortality cardiac, neurologic or cognitive complications, and deterioration in the quality of life. [source] Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (Pif) in rat skinACTA PHYSIOLOGICA, Issue 1 2005V. V. Iversen Abstract Aim:, To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF). Methods:, We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats. Results:, Platelet activating factor (50 ,g mL,1) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 Å, 56 Å and 39 Å after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (Pif) pressure after subcutaneous administration (50 ,g mL,1). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 ,g kg,1) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05). Conclusions:, The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers Pif, indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema. [source] Role of neuronal nitric oxide synthase in response to hypertonic saline loading in ratsACTA PHYSIOLOGICA, Issue 4 2004R. Wangensteen Abstract Aims:, This study analyses the influence of neuronal nitric oxide synthase (nNOS) blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS inhibitor N, -nitro- l -arginine methyl ester (l -NAME). Methods:, The following groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg,1, and rats treated with l -NAME at 0.5 or 5 mg kg,1. A further five groups received an isotonic saline load (ISL). Results:, Mean arterial pressure (MAP) was significantly increased in control rats after HSL. MAP was further increased in both 7NI-treated groups, and the l -NAME groups showed marked dose-related pressor responses. During ISL, MAP was only significantly increased in the group treated with 5 mg kg,1 of l -NAME. The pressure,natriuresis relationship during the experimental period after the HSL was reduced in the 7NI group treated with 5 mg kg,1 and severely attenuated in both l -NAME groups. The increase in plasma sodium was significantly greater after the HSL in both 7NI groups and both l -NAME groups compared with controls. Conclusions:, The present results suggest that nNOS and other NOS isozymes play a counter-regulatory role in the pressor response to HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a blunted pressure,natriuresis relationship in response to the HSL. Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis. [source] Effect of ,-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunumACTA PHYSIOLOGICA, Issue 4 2003A.-M. Lahti Abstract Aim:,d -myo-inositol-1,2,6-trisphosphate (, -trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d -myo-inositol-1,4,5-trisphospahate. The pharmacological actions of , -trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether , -trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum. Methods:, A midline abdominal incision was performed in anaesthetized male Sprague,Dawley rats and a 6,7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass® polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, , -trinositol (60 mg kg,1 h,1) or saline were infused during 2 h, followed by a 2-h control period. Results:, , -Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by , -trinositol. Conclusion:, The inhibition by , -trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction. [source] Influence of neurohumoral blockade on heart rate and blood pressure responses to haemorrhage in isoflurane anaesthetized ratsACTA PHYSIOLOGICA, Issue 3 2000UllmanArticle first published online: 24 DEC 200 Four groups of Sprague,Dawley rats were anaesthetized with isoflurane (ISO) (1.7% end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals were bled 15 mL kg,1 b.w. from the femoral vein over 10 min, followed by an observation period of 30 min. Ten minutes before haemorrhage each group of animals was pre-treated with intravenous injection/infusion of either: isotonic saline (Group B; CON; n=7), vasopressin V1 -receptor antagonist [d(CH2)5Tyr(Me)AVP; 10 ,g kg,1] (Group C; AVP-a; n=7), the non-selective angiotensin II receptor antagonist saralasin (10 ,g kg,1 min,1) (Group D; SAR; n=7) or hexamethonium (10 mg kg,1) (Group E; HEX; n=7). A separate group of conscious animals were pre-treated with isotonic NaCl and subjected to the same haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate (HR) and blood gases were observed during the experiments. Only pre-treatment with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only affected by HEX, which caused a reduction by 17%. The HR was significantly lower at the end of haemorrhage compared with pre-haemorrhage levels in all groups except that group treated with HEX. In that group the HR changed in the opposite direction. The ability to maintain MAP during haemorrhage, and the post-haemorrhage period, was significantly impaired in the groups treated with AVP-a, SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic nervous activity is of major importance for the maintenance of MAP during isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels contribute to a much smaller degree in this regard. General anaesthesia in combination with different degrees of neurohumoral blockade impairs the haemodynamic responses to blood loss, seen in conscious individuals. The impairment involves both the early and late phases during haemorrhage, as well as the post-bleeding recovery period. All three neurohumoral systems (autonomic nervous activity, angiotensin II and vasopressin) are of importance for regulating MAP during and after haemorrhage, although the autonomic nervous outflow appears to contribute to a larger extent. [source] 11b-hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin-II receptor blockadeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2002M. N. Kerstens Abstract Background It has been suggested that an altered setpoint of the 11,HSD-mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11,HSD activity in proteinuric patients, in particular its activity at the kidney level. We also studied the effect of angiotensin-II receptor blockade on the parameters of 11,HSD activity. Materials and methods Serum cortisol/cortisone ratio and the urinary ratios of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone [(THF + allo-THF)/THE] and of urinary free cortisol/free cortisone (UFF/UFE) were measured in eight proteinuric patients and compared with eight matched, healthy subjects. Patients were subsequently studied after 4 weeks' treatment with losartan 50 mg day,1 and placebo, respectively. Results No significant differences between the proteinuric patients and the healthy subjects were observed in the serum cortisol, serum cortisone, serum cortisol to cortisone ratio, or in the urinary excretions of THF, allo-THF, THE, sum of cortisol metabolites, or the (THF + allo-THF)/THE ratio. Urinary free cortisol excretion and the UFF/UFE ratio were lower in the proteinuric patients than in the healthy subjects (56 ± 21 vs. 85 ± 24 pmol min,1, P < 0·05, and 0·39 ± 0·07 vs. 0·63 ± 0·28, P < 0·05, respectively). Mean arterial pressure and proteinuria were reduced significantly during losartan treatment, but without concomitant changes in peripheral cortisol metabolism. Conclusions Increased renal inactivation of cortisol in proteinuric patients does not support the contention that altered 11,HSD activity contributes to sodium retention in patients with nephrotic syndrome. Losartan 50 mg d.d. reduces mean arterial pressure and proteinuria, but does not exert a significant effect on the cortisol to cortisone interconversion. [source] Modulation of systemic and renal haemodynamics by ,-opioids in conscious lambsEXPERIMENTAL PHYSIOLOGY, Issue 5 2006Wei Qi The purpose of the present study was to determine the cardiovascular effects of the ,-opioid receptor agonist U-50488H at two stages of postnatal maturation under physiological conditions. Experiments were carried out firstly to define systemic and renal haemodynamic responses to ,-opioid receptor activation and, secondly, to determine whether these effects are altered during postnatal maturation. To investigate whether the responses to U-50488H resulted from receptor-dependent effects, responses to U-50488H were also tested in the presence of the specific ,-opioid receptor antagonist 5,-guanidinonaltrindole (GNTI). Experiments were carried out in two groups of conscious, chronically instrumented lambs aged ,1 and ,6 weeks. Mean arterial pressure, mean venous pressure and renal blood flow (RBF) were measured for 30 min before and 90 min after i.v. injection of U-50488H or vehicle. Heart rate increased in both age groups of lambs within 10 min of U-50488H administration. Mean arterial pressure decreased for 50 min following U-50488H administration at 1 week but, in contrast, increased transiently at 10 min in 6-week-old lambs, returning to control levels by 20 min. In both age groups, there was a sustained decrease in RBF following U-50488H. The aforementioned responses to U-50488H were abolished by pretreatment with GNTI. These data provide the first measurements of systemic and renal haemodynamic responses to ,-opioid receptor activation during postnatal maturation. [source] Cool dialysate reduces asymptomatic intradialytic hypotension and increases baroreflex variabilityHEMODIALYSIS INTERNATIONAL, Issue 2 2009Lindsay J. CHESTERTON Abstract Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in chronic hemodialysis (HD) patients and can be ameliorated by cool temperature HD. The baroreflex arc is under autonomic control and is essential in the short-term regulation of blood pressure (BP). This study aimed to investigate if the baroreflex sensitivity (BRS) response to HD differed between standard and cool-temperature dialysate. Ten patients (mean age 67±2 years) prone to IDH were recruited into a randomized, crossover study to compare BRS variation at dialysate temperatures of 37 °C (HD37) and 35 °C (HD35). Each patient underwent continuous beat-to-beat BP monitoring during a dialysis session of HD37 and HD35. During HD37 2 patients developed symptomatic IDH, as opposed to 1 with HD35. However, asymptomatic IDH occurred with a frequency of 0.4 episodes per session with HD35 and 6.2 episodes per session during HD37 (odds ratio15.5; 95%CI 5.6,14.2). Although absolute BRS measurements did not differ between the 2 modalities, BRS variability increased during HD35. Our study has demonstrated that in IDH-prone patients, cool HD resulted in a reduction in heart rate and a greater reduction in cardiac output and stroke volume. Mean arterial pressure was maintained through a significantly greater increase in total peripheral resistance. Furthermore, although absolute BRS values during HD were not significantly altered by a reduction in dialysate temperature, there was a greater percentage increase in BRS values during cool HD. Understanding the varied causes of, and categorizing impaired hemodynamic responses to HD will enable further individualization of HD prescriptions according to patient need. [source] Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressinHEPATOLOGY RESEARCH, Issue 10 2010George Kalambokis Aim:, The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment. Methods:, Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium-99m -labeled macroaggregated albumin (99mTc-MAA) and calculation of brain uptake (positive value ,6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography. Results:, Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child,Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01). Conclusion:, IPS fractions detected by 99mTc-MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt. [source] Anaesthetic requirement and stress hormone responses in patients undergoing lumbar spine surgery: anterior vs. posterior approachACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009K. Y. YOO Background: The intensity of nociceptive stimuli reflects the severity of tissue injury. The anaesthetic requirement and stress hormonal responses were determined to learn whether they differ according to different surgical approaches (anterior vs. posterior) during the spinal surgery. Methods: Patients undergoing lumbar spine surgery without neurological deficits were divided into two groups: one having posterior (n=13) and the other having anterior fusion (n=13). The end-tidal sevoflurane concentrations (ETSEVO) required to maintain the bispectral index score at 40,50 were determined. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum osmolality and plasma concentrations of catecholamines, cortisol and vasopressin (AVP) were measured. Results: There were no differences in MAP, HR, CVP and serum osmolality between the groups. ETSEVO was higher in the anterior than in the posterior group (P<0.05). The plasma concentrations of norepinephrine and cortisol increased in both groups during the surgery, whereas those of epinephrine remained unchanged. AVP concentrations increased during the surgery in the anterior group, and remained unaltered in the posterior group. The anterior group needed more analgesics (P<0.01) during the first 1 h after the operation. Conclusions: The anterior approach required a deeper level of anaesthesia while undergoing spinal surgery and more use of post-operative analgesics than the posterior approach. It was also associated with a more pronounced AVP release during the surgery. [source] Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overloadJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010María I. Rosón The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague,Dawley rats were infused for 2,h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10,mg,kg,1 in bolus) (Na,Los group), or plus the superoxide dismutase mimetic tempol (0.5,mg,min,1,kg,1) (Na,Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FENa) were measured. Ang II, NF-,B, hypoxia inducible factor-1, (HIF-1,), transforming growth factor ,1 (TGF-,1), smooth muscle actin (,-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-,B, and TGF-,1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1, immunostaining, lower eNOS expression, and unmodified ,-SMA. Losartan and tempol increased FENa in sodium overload group. Although losartan reduced Ang II and NF-,B staining and increased eNOS expression, it did not restore HIF-1, expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1, expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1, and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1, expression and down-regulating TGF-,1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. J. Cell. Physiol. 224:41,48, 2010 © 2010 Wiley-Liss, Inc. [source] Heritability of the Blood Pressure Response to Acute Ethanol Exposure in Five Inbred Strains of MiceALCOHOLISM, Issue 10 2000Daniel C. Hatton Background: Chronic alcohol consumption is a major risk factor for hypertension. There is evidence in humans that the susceptibility to alcohol-related hypertension may vary based on genotype. As a first step in investigating the genetic basis for alcohol-related hypertension, the current study was designed to assess the heritability of the blood pressure response to acute ethanol exposure by using AKR/J (AK), C57BL/6J (B6), DBA/2J (D2), Balb/cJ (Balb), and A/J (A) mice. Methods: Mean arterial pressure (MAP) was recorded continuously for 24 hr in freely moving mice from an indwelling femoral catheter before we tested the effects of saline or ethanol (2 g/kg ip) on blood pressure. Results: Relative to saline, ethanol caused a pressor response that peaked within 10 min, followed by a decline in MAP. Strain A mice had a significantly greater pressor response to ethanol than other strains and did not show a decline in MAP below baseline. All other strains showed a progressive fall in blood pressure below baseline across the 60 min measurement interval. Heritability was estimated to be 0.62 for the pressor response and 0.64 for the maximal depressor response. Repeated doses of ethanol at 1 hr intervals in A and B6 mice (0,2,1.5,1.5,1.5 g/kg ip) resulted in a dose-dependent increase in MAP in A mice for the first three doses and a dose-dependent decrease in MAP in B6 mice that was independent of blood ethanol concentrations. Conclusion: The results indicate that there is a significant genetic component to the acute blood pressure response to ethanol. [source] The effects of ketamine and propofol on bacterial translocation in rats after burn injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2005H. Yagmurder Background:, Bacterial translocation (BT) occurs after thermal injury and may result from an ischemic intestinal insult. The aim of the study was to investigate the effects of ketamine and propofol as anesthetic agents on BT in an animal model of burn injury. Methods:, Sixty male Wistar Albino rats were randomly assigned to six groups of 10 rats each. Anesthesia was induced and maintained with ketamine in groups 1, 2 and 3 and with propofol in groups 4, 5 and 6 during 6 h. Groups 2, 3, 5 and 6 received 30% total body surface area (TBSA) third-degree burns. Groups 1 and 4 had no burn injury. Then, they were allowed to recover from the anesthesia at the end of 6 h. Mean arterial pressure (MAP) was monitored continuously and maintained within 10% of baseline (before burn injury) levels in all animals. Animals in groups 3 and 6 had a laparotomy to obtain a tissue sample from the terminal ileum for determination of intestinal lipid peroxidation by-product malondialdehyde (MDA) before (baseline) and 6 and 24 h after burn injury (ABI). So these animals were not included in the BT studies. At postburn 24 h, animals in groups 1, 2 and 4, 5 were sacrified and samples were taken from the mesenteric lymph nodes (MLN), liver and spleen for bacteriologic cultures. Results:, The incidence of BT was found to be significantly higher in group 2 than in all the other groups. Bacterial translocation incidence of group 5 was not significantly different from that of groups 4 and 1. Group 5 was associated with a significantly reduced number of enteric organisms per gram of tissue compared to group 2. Baseline MDA contents of groups 3 and 6 were similar. Ileal MDA levels were increased in group 3, but there were no significant changes in group 6 at 6 and 24 h ABI compared to baseline. Conclusion:, Our results suggest that propofol as an anesthetic agent may prevent BT by scavenging reactive oxygen species and inhibiting lipid peroxidation in an animal model of burn injury. [source] Reverse flow facial artery as recipient vessel for perforator flapsMICROSURGERY, Issue 6 2009D.D.S., Frank Hölzle M.D., Ph.D. In perforator flaps, anastomosis between flap and recipient vessels in the neck area is often difficult due to small vessel diameter and short pedicle. The aim of this study was to investigate whether the retrograde flow of the distal, paramandibular part of the facial artery would provide sufficient pressure and size to perfuse perforator flaps. Before and after occlusion of the contralateral facial artery, retrograde and anterograde arterial pressure was measured on both sides of the facial artery in 50 patients. The values were compared with the mean systemic arterial pressure. Diameters of facial arteries in the paramandibular region and perforator flap vessels were evaluated by morphometry. Arterial pressure in the distal facial artery with retrograde flow was 76% of the systemic arterial pressure. The latter equaled approximately the anterograde arterial pressure in the proximal end of the facial artery. Mean arterial pressure of the facial arteries decreased after proximal occlusion of the contralateral facial artery, which was not significant (P = 0.09). Mean diameter of the distal facial arteries in the mandibular region was 1.6 mm (range 1.3,2.2 mm; standard deviation 0.3 mm; n = 50), that of the perforator flap arteries 1.3 mm (0.9,2.6 mm; 0.4 mm; n = 20). Facial arteries, based on reverse flow, successfully supported all 20 perforator flaps. Retrograde pulsatile flow in the distal facial artery sustains perforator flaps even if the contralateral facial artery is occluded. Proximity of the distal facial arteries to the defect compensates for short pedicles. Matching diameters of the arteries are ideal for end-to-end anastomosis. © 2009 Wiley-Liss, Inc. Microsurgery, 2009. [source] Effect of adrenergic stimulation on cutaneous microcirculation immediately after surgical adventitiectomy in a rat skin flap modelMICROSURGERY, Issue 6 2008Jean-Pierre H. Lecoq M.D. Chronic sympathetic denervation leads to the development of supersentivity to adrenergic agents. Free flap surgery results in the disruption of the autonomic nerve fibers running along the anastomosed vessels. We therefore investigated the early effect of surgical sympathectomy on the reactivity of cutaneous microcirculation challenged to adrenergic agents. Two epigastric flaps were elevated and exposed in 15 rats. On the right flap (Side A), a circular adventitiectomy of the feeder vessels was realized to provide surgical sympathectomy. On the left flap (Side N), vessels were kept intact. The following drugs were then given intravenously successively: phenylephrine (10 and 15 ,g kg,1), norepinephrine (10 ,g kg,1), prazocin (1 mg kg,1) followed by norepinephrine (10 ,g kg,1). Cutaneous microcirculation was assessed using Laser-Doppler Flowmeters simultaneously on the two flaps after each drug administration. Mean arterial pressure was also measured. On side N, phenylephrine and norepinephrine resulted in a transient increase in cutaneous microcirculation followed by a more prolonged reduction. On side A, only the initial increase was observed, which was greater and longer as compared with side N, and paralleled the increase in mean arterial pressure. After prazocin pre-treatment, norepinephrine produced a transient increase in cutaneous microcirculation similar on both sides, and parallel to the changes in arterial pressure. No decrease in cutaneous microcirculation was observed. Immediately after surgical adventitiectomy, the vasoconstriction produced by ,-adrenergic agents is prevented. No denervation-induced hypersentivity is observed. Surgical sympathectomy might protect cutaneous flaps from vasoconstriction induced by endogenous catecholamines release. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source] Initial Experience with a New Right Ventricular Support Device for Beating Heart SurgeryARTIFICIAL ORGANS, Issue 1 2004Ferdinand Kuhn-Régnier Abstract:, Objective: Device supported beating heart surgery has been advocated to extend patient selection criteria for off-pump surgery. This article reports the initial experimental and clinical results with a novel paracardial right ventricular support device. Methods: Preclinical experiments were performed in two pigs. Ten elective patients with triple vessel disease were subjected to beating heart coronary artery bypass grafting surgery during right ventricular support by the paracardial device. Measurements included intraoperative hemodynamics during cardiac tilting, perioperative left ventricular ejection fraction (LVEF), hemolysis parameters, mortality and major morbidity events. Results: A mean of 3.2 ± 0.2 distal anastomoses per patient were performed. Mean arterial pressure and central venous oxygen saturation remained stable during cardiac tilting. Perioperative LVEF did not vary significantly. Sixty-day mortality and postoperative infarction rate were 0%. Functional Canadian Cardiovascular Society class at 6 days after surgery was 1.2 ± 0.1 vs. 3.3 ± 0.2 pre-operatively. Conclusion: In this initial clinical experience, application of the novel paracardial right ventricular support device proved ,to be safe and efficient. [source] Centrifugal Pump Support for Distal Aortic Perfusion During Repair of Traumatic Thoracic Aortic InjuryARTIFICIAL ORGANS, Issue 11 2002Joseph T. Walls Abstract: Paraplegia from ischemic injury of the spinal cord and renal failure from inadequate perfusion of the kidneys may occur from aortic cross-clamping during repair of traumatic thoracic aortic injuries. After Institutional Review Board approval, we retrospectively reviewed the charts of 26 patients surgically treated for traumatic transection of the descending thoracic aorta during a 14 year period (1987,2001), using centrifugal pump (Sarns) support for distal aortic perfusion. The study group comprised 19 males and 7 females, whose ages ranged from 15 to 69 years. For all but 1 patient, who fell from a flagpole, the injuries were incurred in motor vehicle accidents. Aortic cross-clamp time lasted between 5 to 78 min (median = 40 min). Mean arterial pressure ranged from 50 to 80 mm Hg (median = 70 mm Hg). All patients survived operation without developing paraplegia or renal failure. Distal centrifugal pump perfusion during repair of traumatic injury of the descending thoracic aorta is a valuable adjunct during surgical treatment and aids in preservation of spinal cord and renal function. [source] Correlation of Plasma and Peritoneal Diasylate Clomipramine Concentration with Hemodynamic Recovery after Intralipid Infusion in RabbitsACADEMIC EMERGENCY MEDICINE, Issue 2 2009MBChB, Martyn Harvey FACEM Abstract Objectives:, Drug sequestration to an expanded plasma lipid phase has been proposed as a potential mechanism of action for lipid emulsions in lipophilic cardiotoxin overdose. The authors set out to document plasma and peritoneal diasylate clomipramine concentration after resuscitation with lipid emulsion in a rabbit model of clomipramine-induced hypotension. Methods:, Twenty sedated mechanically ventilated New Zealand White rabbits were allocated to receive either 12 mL/kg 20% Intralipid or 12 mL/kg saline solution, following clomipramine infusion to 50% baseline mean arterial pressure (MAP). Hemodynamic parameters and serum clomipramine concentration were determined to 59 minutes. Peritoneal dialysis with 20% Intralipid or saline solution was evaluated for clomipramine concentration. Results:, Mean arterial pressure was greater in lipid-treated animals as assessed by repeated-measures analysis of variance (F[1,14] = 6.84; p = 0.020). Lipid infusion was associated with elevated plasma clomipramine concentration and reduced initial volume of distribution (Vd; 5.7 [±1.6] L/kg lipid vs. 15.9 [±7.2] L/kg saline; p = 0.0001). Peritoneal diasylate clomipramine concentration was greater in lipid-treated animals (366.2 [±186.2] ,g/L lipid vs. 37.7 [±13.8] ,g/L saline; p = 0.002). Conclusions:, Amelioration of clomipramine-induced hypotension with lipid infusion is associated with reduced initial Vd and elevated plasma clomipramine concentration consistent with intravascular drug,lipid sequestration. Concomitant peritoneal dialysis with lipid emulsion enhances clomipramine extraction. [source] Eight Hours of Hypotensive versus Normotensive Resuscitation in a Porcine Model of Controlled Hemorrhagic ShockACADEMIC EMERGENCY MEDICINE, Issue 9 2008David E. Skarda MD Abstract Objectives:, The aim of this study was to compare hypotensive and normotensive resuscitation in a porcine model of hemorrhagic shock. Methods:, This was a prospective, comparative, randomized survival study of controlled hemorrhagic shock using 28 male Yorkshire-Landrace pigs (15 to 25 kg). In 24 splenectomized pigs, the authors induced hemorrhagic shock to a systolic blood pressure (sBP) of 48 to 58 mm Hg (,35% bleed). Pigs were randomized to undergo normotensive resuscitation (sBP of 90 mm Hg, n = 7), mild hypotensive resuscitation (sBP of 80 mm Hg, n = 7), severe hypotensive resuscitation (sBP of 65 mm Hg, n = 6), or no resuscitation (n = 4). The authors also included a sham group of animals that were instrumented and splenectomized, but that did not undergo hemorrhagic shock (n = 4). After the initial 8 hours of randomized pressure-targeted resuscitation, all animals were resuscitated to a sBP of 90 mm Hg for 16 hours. Results:, Animals that underwent severe hypotensive resuscitation were less likely to survive, compared with animals that underwent normotensive resuscitation. Mean arterial pressure (MAP) decreased with hemorrhage and increased appropriately with pressure-targeted resuscitation. Base excess (BE) and tissue oxygen saturation (StO2) decreased in all animals that underwent hemorrhagic shock. This decrease persisted only in animals that were pressure target resuscitated to a sBP of 65 mm Hg. Conclusions:, In this model of controlled hemorrhagic shock, initial severe hypotensive pressure-targeted resuscitation for 8 hours was associated with an increased mortality rate and led to a persistent base deficit (BD) and to decreased StO2, suggesting persistent metabolic stress and tissue hypoxia. However, mild hypotensive resuscitation did not lead to a persistent BD or to decreased StO2, suggesting less metabolic stress and less tissue hypoxia. [source] Relevance of the C-terminal Arg-Phe sequence in ,2 -melanocyte-stimulating hormone (,2 -MSH) for inducing cardiovascular effects in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000M J M A Nijsen The cardiovascular effects by ,2 -melanocyte-stimulating hormone (,2 -MSH) are probably not due to any of the well-known melanocortin subtype receptors. We hypothesize that the receptor for Phe-Met-Arg-Phe-amide (FMRFa) or Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide (neuropeptide FF; NPFFa), other Arg-Phe containing peptides, is the candidate receptor. Therefore, we studied various Arg-Phe containing peptides to compare their haemodynamic profile with that of ,2 -MSH(6,12), the most potent fragment of ,2 -MSH. Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after intravenous administration of ,2 -MSH related peptides. Phe-Arg-Trp-Asp-Arg-Phe-Gly (,2 -MSH(6,12)), FMRFa, NPFFa, Met-enkephalin-Arg-Phe-amide (MERFa), Arg-Phe-amide (RFa), acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa) and desamino-Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa) caused a dose-dependent increase in MAP and HR. ,2 -MSH(6,12) showed the most potent cardiovascular effects (ED50=12 nmol kg,1 for ,MAP; 7 nmol kg,1 for ,HR), as compared to the other Arg-Phe containing peptides (ED50=177,292 nmol kg,1 for ,MAP; 130,260 nmol kg,1 for ,HR). Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Pro-Gly (,2 -pro11 -MSH), desamino-Tyr-Phe-norLeu-Arg-[L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid]-amide (daYFnLR[TIC]a) and Met-enkephalin (ME)), were devoid of cardiovascular actions. The results indicate that the baroreceptor reflex-mediated reduction of tonic sympathetic activity due to pressor effects is inhibited by ,2 -MSH(6,12) and that its cardiovascular effects are dependent on the presence of a C-terminal Arg-Phe sequence. It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular effects. British Journal of Pharmacology (2000) 131, 1468,1474; doi:10.1038/sj.bjp.0703709 [source] Haemodynamic action of B-type natriuretic peptide substantially outlasts its plasma half-life in conscious dogsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2003Colleen J Thomas Summary 1.,The objective of the present study was to determine the plasma half-life of B-type natriuretic peptide (BNP) in conscious dogs after intravenous administration and to compare this with its haemodynamic effects. In six chronically instrumented dogs, plasma BNP concentrations were measured under basal conditions, during a constant infusion of canine BNP-32 (10 pmol/kg per min; 25 min) to steady state and at nominated time points up to 75 min after stopping the infusion. Concomitant, continuous measurements of mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP) and mesenteric blood flow (MBF) were obtained. 2.,Baseline plasma BNP levels were 15.0 ± 2.3 fmol/mL and rose approximately 10-fold to 159 ± 23 fmol/mL after 20,25 min BNP infusion. When the infusion was turned off, plasma BNP levels declined in a biphasic manner, with an initial half-life of 1.57 ± 0.14 min and a terminal half-life of 301 ± 85 min. The metabolic clearance rate of BNP was 2.29 ± 0.34 L/min. 3.,The infusion of BNP reduced MAP (approximately 10%), CVP (approximately 65%) and MBF (approximately 25%), whereas haematocrit (approximately 4%) and mesenteric vascular resistance (MVR) increased (approximately 40%; all P < 0.05). Plasma BNP levels returned to baseline by 20 min after BNP infusion had been stopped, whereas none of the haemodynamic variables returned to normal by this time. Mean arterial pressure returned to resting levels within 10,15 min after plasma BNP returned to normal. However, CVP, haematocrit and MBF remained substantially below baseline values for more than 20 min after circulating BNP levels had returned to pre-infusion levels. Of these, only mesenteric vascular changes were returned to baseline within 60 min of plasma BNP levels normalizing. 4.,These results demonstrate that the removal of BNP from the canine circulation is rapid, similar to observations made regarding the metabolism of circulating atrial natriuretic peptide in dogs. The half-life of BNP in dogs was shorter than that in rats, sheep or humans. However, the haemodynamic actions of BNP substantially outlasted its plasma half-life. Whether this disparity in plasma level and haemodynamic activity of BNP reflects long-lasting activation of second messenger systems or slow recovery from the hydraulic changes at the capillary level, reflected in the haematocrit and CVP, remains to be answered. [source] Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2003HR De Smet Summary 1.,Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2.,In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3.,In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4.,Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5.,We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo. [source] Renal And Cardiac Sympathetic Baroreflexes In Hypertensive RabbitsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001Geoffrey A Head SUMMARY 1. The purpose of the present study was to assess the changes to renal sympathetic nerve activity (RSNA) baroreflexes during the development of hypertension after renal clipping in conscious rabbits. 2. Rabbits were fitted with a clip on the right renal artery or underwent a sham operation under halothane anaesthesia. A recording electrode was implanted on the left renal nerve 1 week before the experiment, 3 or 6 weeks after the initial operation. During the experiment, drug-induced ramp rises and falls in mean arterial pressure (MAP) were used to produce RSNA and heart rate (HR) baroreflex curves. The RSNA for each experiment was calibrated against maximum RSNA evoked by stimulation of baroreceptor-independent trigeminal afferents. 3. Mean arterial pressure was 20 and 36% higher 3 and 6 weeks after clip implantation, respectively. Renal sympathetic nerve activity baroreflex curves were reset rightwards accordingly, but the shape of the RSNA curves was differentially affected. 4. At both hypertensive periods, MAP,HR baroreflex gain was markedly reduced due to a reduction in curvature. The HR baroreflex range was increased. The RSNA baroreflex gain was reduced at 3 weeks, which was due to a 35% lower RSNA baroreflex range, but was similar to sham animals at 6 weeks. 5. The results show that, in established two kidney, one clip hypertension in rabbits, the sympathetic baroreflex is relatively well preserved but sensitivity of cardiac baroreflexes is attenuated. Therefore, the short-term inhibition of RSNA baroreflexes is not related to the level of blood pressure or the development of secondary changes, such as cardiac or vascular hypertrophy, but may be related to circulating angiotensin, which is known to increase at this time. [source] Validation of a screening protocol for identifying low-risk candidates with type 1 diabetes mellitus for kidney with or without pancreas transplantationCLINICAL TRANSPLANTATION, Issue 2 2006Irene W.Y. Ma Abstract: Background: Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post-transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high-risk transplant candidates. Methods: All patients with type 1 diabetes evaluated between 1991 and 2001 for kidney with/without pancreas transplantation were classified as high-risk based on the presence of any of the following risk factors: age ,45 yr, smoking history ,5 pack years, diabetes duration ,25 yr or any ST,T segment abnormalities on electrocardiogram. Remaining patients were considered low risk. All high-risk candidates were advised to undergo coronary angiography. The primary outcome of interest was all-cause mortality post-transplantation. Results: Eighty-four high-risk and 42 low-risk patients were identified. Significant coronary artery stenosis was detected in 31 high-risk candidates. Mean arterial pressure was a significant predictor of coronary stenosis (odds ratio 1.68; 95% confidence interval 1.14,2.46), adjusted for age, sex and duration of diabetes. In 75 candidates who underwent transplantation with median follow-up of 47 months, the use of clinical risk factors predicted all eight deaths. No deaths occurred in low-risk patients. A significant mortality difference was noted between the two risk groups (p=0.03). Conclusions: This clinical algorithm can identify patients with type 1 diabetes at risk for mortality after kidney with/without pancreas transplant. Patients without clinical risk factors can safely undergo transplantation without further cardiac evaluation. [source] Human cutaneous reactive hyperaemia: role of BKCa channels and sensory nervesTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Santiago Lorenzo Reactive hyperaemia is the increase in blood flow following arterial occlusion. The exact mechanisms mediating this response in skin are not fully understood. The purpose of this study was to investigate the individual and combined contributions of (1) sensory nerves and large-conductance calcium activated potassium (BKCa) channels, and (2) nitric oxide (NO) and prostanoids to cutaneous reactive hyperaemia. Laser-Doppler flowmetry was used to measure skin blood flow in a total of 18 subjects. Peak blood flow (BF) was defined as the highest blood flow value after release of the pressure cuff. Total hyperaemic response was calculated by taking the area under the curve (AUC) of the hyperaemic response minus baseline. Infusates were perfused through forearm skin using microdialysis in four sites. In the sensory nerve/BKCa protocol: (1) EMLA® cream (EMLA, applied topically to skin surface), (2) tetraethylammonium (TEA), (3) EMLA®+ TEA (Combo), and (4) Ringer solution (Control). In the prostanoid/NO protocol: (1) ketorolac (Keto), (2) NG -nitro- l -arginine methyl ester (l -NAME), (3) Keto +l -NAME (Combo), and (4) Ringer solution (Control). CVC was calculated as flux/mean arterial pressure and normalized to maximal flow. Hyperaemic responses in Control (1389 ± 794%CVCmax s) were significantly greater compared to TEA, EMLA and Combo sites (TEA, 630 ± 512, P= 0.003; EMLA, 421 ± 216, P < 0.001; Combo, 201 ± 200, P < 0.001%CVCmax s). Furthermore, AUC in Combo (Keto +l -NAME) site was significantly greater than Control (4109 ± 2777 versus 1295 ± 368%CVCmax s). These data suggest (1) sensory nerves and BKCa channels play major roles in the EDHF component of reactive hyperaemia and appear to work partly independent of each other, and (2) the COX pathway does not appear to have a vasodilatory role in cutaneous reactive hyperaemia. [source] Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skinTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Brett J. Wong The neuropeptide substance P is known to be localized in nerve terminals in human skin and substance P-induced vasodilatation is believed to be partially dependent on nitric oxide (NO) and H1 histamine receptor activation. Unlike other neuropeptides investigated in human skin, substance P-induced vasodilatation has been shown to decline during continuous infusion, possibly suggestive of an internalization of neurokinin-1 (NK1) receptors, which are highly specific to substance P. However, questions remain regarding these mechanisms in human skin. Fifteen subjects participated in this series of studies designed to investigate the effect of consecutive infusions and possible mechanisms of substance P-induced vasodilatation in human skin. Two concentrations of substance P (10 ,m and 20 ,m) were tested via intradermal microdialysis in two groups of subjects. Site 1 served as a control and received substance P only. Site 2 received substance P combined with 10 mm l -NAME to inhibit NO synthase. Site 3 received substance P combined with 500 ,m pyrilamine, an H1 receptor antagonist. Site 4 received substance P combined with 10 mm l -NAME plus 500 ,m pyrilamine. Red blood cell (RBC) flux was measured via laser-Doppler flowmetry to provide an index of skin blood flow. Cutaneous vascular conductance was calculated as RBC flux/mean arterial pressure and was normalized to maximal vasodilatation via 28 mm sodium nitroprusside. Substance P was perfused through each microdialysis fibre at a rate of 4 ,l min,1 for 15 min. The subsequent increase in skin blood flow was allowed to return to baseline (,45,60 min) and a stable 5 min plateau was used as a new baseline (post-infusion baseline). A second dose of substance P was then delivered to the skin and skin blood flow was monitored for 45,60 min. Substance P produced a dose-dependent increase in skin blood flow with the concentrations of substance P tested, which was significantly attenuated in the presence of l -NAME and the combination of l -NAME plus pyrilamine. However, substance P-induced vasodilatation was unaffected in the presence of pyrilamine. There was no significant difference between the l -NAME-only sites and the l -NAME plus pyrilamine sites. Importantly, the second dose of substance P did not produce a significant increase in skin blood flow compared to the initial baseline or the post-infusion baseline. These data suggest substance P-induced vasodilatation delivered via microdialysis contains an NO component but does not contain an H1 receptor activation component at the doses tested. Additionally, these data provide evidence for NK1 receptor desensitization as there was no observable increase in skin blood flow following a second administration of substance P. This may provide a useful model for studying the role of substance P in the control of skin blood flow in humans. [source] Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skinTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Lacy A. Holowatz Thermoregulatory cutaneous vasodilatation (VD) is attenuated in aged skin. While acetylcholine (ACh) plays a role in thermally mediated VD, the precise mechanisms through which ACh-mediated VD acts and whether those downstream mechanisms change with ageing are unclear. We tested the hypotheses that both nitric oxide (NO)- and prostanoid-mediated pathways contribute to exogenous ACh-mediated VD, and that both are attenuated with advanced age. Twelve young (Y: 23 ± 1 years) and 10 older (O: 69 ± 1 years) subjects underwent infusions of 137.5 ,m ACh at four intradermal microdialysis sites: control (C, Ringer solution), NO synthase inhibited (NOS-I, 10 mml -NAME), cyclooxygenase inhibited (COX-I, 10 mm ketorolac) and NOS-I + COX-I. Red blood cell flux was monitored using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (laser-Doppler flux/mean arterial pressure) and normalized to maximal CVC (%CVCmax) (28 mm sodium nitroprusside + local heating to 43°C). Baseline %CVCmax was increased in the O at COX-I sites (COX-I 16 ± 1, NOS-I + COX-I 16 ± 2 versus C 10 ± 1%CVCmax; P < 0.001) but not in the young, suggesting an age-related shift toward COX vasoconstrictors contributing to basal cutaneous vasomotor tone. There was no difference in peak %CVCmax during ACh infusion between age groups, and the response was unchanged by NOS-I (O: NOS-I 35 ± 5 versus C 38 ± 5%CVCmax; P= 0.84) (Y: NOS-I 41 ± 4 versus C 39 ± 4%CVCmax; P= 0.67). COX-I and NOS-I + COX-I attenuated the peak CVC response to ACh in both groups (COX-I O: 29 ± 3, Y: 22 ± 2%CVCmaxversus C; P < 0.001 both groups; NOS-I + COX-I O: 32 ± 3 versus Y: 29 ± 2%CVCmax; versus C; P < 0.001 both groups). ACh mediates cutaneous VD through prostanoid and non-NO-, non-prostanoid-dependent pathways. Further, older subjects have a diminished prostanoid contribution to ACh-mediated VD. [source] | ||||||||||||||||||||||||||||||||||