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Vascular Reactivity (vascular + reactivity)
Kinds of Vascular Reactivity Selected AbstractsCOMPARATIVE EFFECTS OF TRAMADOL ON VASCULAR REACTIVITY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008Juliana M Raimundo SUMMARY 1The aim of the present study was to determine the effects of tramadol on vascular reactivity in aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2Aortic rings, with or without endothelium, were obtained from male WKY rats and SHR (15,20 weeks old) and prepared for isometric tension recording. Aortic rings were precontracted with phenylephrine (10 µmol/L) or 40 mmol/L KCl and then exposed to cumulative concentrations of tramadol (0.1,1 mmol/L). 3Tramadol produced a concentration-dependent relaxation of precontracted aortic rings from WKY rats and SHR, which was not dependent on functional endothelium. Vascular relaxation was significantly greater in rings from SHR than WKY rats. 4The concentration of tramadol necessary to produce a 50% reduction of the maximal contraction to phenylephrine (IC50) in rings with and without endothelium from SHR was 0.47 ± 0.08 and 0.44 ± 0.03 mmol/L, respectively (P = 0.76). 5Tramadol attenuated the contracture elicited by Ca2+ in depolarized tissue, suggesting that it may inhibit L-type Ca2+ channels. However, pretreatment with nicardipine (1 µmol/L) prevented the relaxation induced by tramadol in aortic rings from WKY rats and partially reduced its inhibitory effect in aortic rings from SHR. 6Pretreatment of endothelium-denuded aorta with glybenclamide (3 µmol/L), 4-aminopyridine (3 mmol/L), tetraethylammonium (3 mmol/L) and naloxone (100 µmol/L) did not affect tramadol-induced vasodilation of aortic rings from either WKY rats or SHR. 7Intravenous administration of tramadol (10 mg/kg) to conscious SHR significantly reduced both systolic and diastolic blood pressure from 171.4 ± 5.3 to 129.3 ± 5.3 (P = 0.002) and from 125.0 ± 6.5 to 57.8 ± 8.9 mmHg (P = 0.003), respectively. [source] Vascular reactivity to angiotensin II alone or combined with a thromboxane A2 mimetic in the isolated perfused kidney of Lyon hypertensive ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2002Valérie Oréa The aim of this study was to evaluate whether thromboxane A2 -prostaglandin H2 (TP) receptor activation potentiates the renal vasoconstrictor effect of Angiotensin II (Ang II) in genetically hypertensive rats of the Lyon strain (LH). Concentration-response curves (CRCs) to Ang II (5 pM to 10 nM), to the specific TP receptor agonist U46619 (7.5,960 nM) and to a mixture of Ang II + U46619 (fixed molar ratio of 1 : 9) were obtained in single-pass perfused kidneys isolated from 8 week-old LH and low blood pressure (LL) control rats. Baseline vascular resistance was significantly increased in LH compared to LL kidneys. Comparison of the CRCs obtained for Ang II and U46619 showed that, in both strains, Ang II was about 100 times more potent than U46619. For both drugs, the pD2 or slope values did not differ among the two strains. Co-activation of TP receptors, analyzed with the method of Pöch and Holzmann, tended to potentiate the effects of Ang II in LH but not in LL kidneys. In conclusion, isolated perfused kidneys of LH rat did not exhibit an increased vascular sensitivity to acute infusion of Ang II or U46619 compared to control LL ones. In addition, the results suggest that the interactions between Ang II and TP receptor agonist may differ among the two strains. [source] Adenosine A1 receptors and vascular reactivityACTA PHYSIOLOGICA, Issue 2 2010Y. Wang Abstract Aim:, Blood pressure is higher in A1 receptor knock-out (A1R,/,) mice than in wild type litter mates (A1R+/+) and we have examined if this could be related to altered vascular functions. Methods:, Contraction of aortic rings and mesenteric arteries were examined. To examine if the adenosine A1 receptor-mediated contraction of aortic muscle was functionally important we examined pulse pressure (PP) and augmentation index (AIX) using a sensor that allows measurements of rapid pressure transients. Results:, Contraction of aortic rings to phenylephrine and relaxation to acetylcholine were similar between genotypes. The non-selective adenosine receptor agonist N -ethyl carboxamido adenosine (NECA) enhanced the contractile response, and this was eliminated in aortas from A1R,/, mice. However, in mesenteric arteries no contractile response was seen and adenosine-mediated relaxation was identical between studied genotypes. A2B adenosine receptors, rather than A2A receptors, may be mainly responsible for the vasorelaxation induced by adenosine analogues in the examined mouse vessels. PP was higher in A1R,/, mice, but variability was unaltered. AIX was not different between genotypes, but the NECA-induced fall was larger in A1R,/, mice. Conclusions:, The role of adenosine A1 receptors in regulating vessel tone differs between blood vessels. Furthermore, contractile effects on isolated vessels cannot explain the blood pressure in A1 knock-out mice. The A1 receptor modulation of blood pressure is therefore mainly related to extravascular factors. [source] Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular diseaseACTA PHYSIOLOGICA, Issue 1 2010D. Lominadze Abstract Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. [source] Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseasesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2006Eugenio Cersosimo Abstract Cardiovascular disease affects approximately 60% of the adult population over the age of 65 and represents the number one cause of death in the United States. Coronary atherosclerosis is responsible for the vast majority of the cardiovascular events, and a number of cardiovascular risk factors have been identified. In recent years, it has become clear that insulin resistance and endothelial dysfunction play a central role in the pathogenesis of atherosclerosis. Much evidence supports the presence of insulin resistance as the fundamental pathophysiologic disturbance responsible for the cluster of metabolic and cardiovascular disorders, known collectively as the metabolic syndrome. Endothelial dysfunction is an important component of the metabolic or insulin resistance syndrome and this is demonstrated by inadequate vasodilation and/or paradoxical vasoconstriction in coronary and peripheral arteries in response to stimuli that release nitric oxide (NO). Deficiency of endothelial-derived NO is believed to be the primary defect that links insulin resistance and endothelial dysfunction. NO deficiency results from decreased synthesis and/or release, in combination with exaggerated consumption in tissues by high levels of reactive oxygen (ROS) and nitrogen (RNS) species, which are produced by cellular disturbances in glucose and lipid metabolism. Endothelial dysfunction contributes to impaired insulin action, by altering the transcapillary passage of insulin to target tissues. Reduced expansion of the capillary network, with attenuation of microcirculatory blood flow to metabolically active tissues, contributes to the impairment of insulin-stimulated glucose and lipid metabolism. This establishes a reverberating negative feedback cycle in which progressive endothelial dysfunction and disturbances in glucose and lipid metabolism develop secondary to the insulin resistance. Vascular damage, which results from lipid deposition and oxidative stress to the vessel wall, triggers an inflammatory reaction, and the release of chemoattractants and cytokines worsens the insulin resistance and endothelial dysfunction. From the clinical standpoint, much experimental evidence supports the concept that therapies that improve insulin resistance and endothelial dysfunction reduce cardiovascular morbidity and mortality. Moreover, interventional strategies that reduce insulin resistance ameliorate endothelial dysfunction, while interventions that improve tissue sensitivity to insulin enhance vascular endothelial function. There is general agreement that aggressive therapy aimed simultaneously at improving insulin-mediated glucose/lipid metabolism and endothelial dysfunction represents an important strategy in preventing/delaying the appearance of atherosclerosis. Interventions that 1 correct carbohydrate and lipid metabolism, 2 improve insulin resistance, 3 reduce blood pressure and restore vascular reactivity, and 4 attenuate procoagulant and inflammatory responses in adults with a high risk of developing cardiovascular disease reduce cardiovascular morbidity and mortality. Whether these benefits hold when the same prevention strategies are applied to younger, high-risk individuals remains to be determined. Copyright © 2006 John Wiley & Sons, Ltd. [source] Abnormal vascular reactivity at rest and exercise in obese boysEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2009L. Karpoff Abstract Background, Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild-to-moderate obesity and in lean controls. Materials and methods, Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m,2)] and thirteen controls (BMI:17·4 ± 1·8 kg m,2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima-media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow-mediated dilation (FMD) and nitrate-dependent dilation (NDD), lower limb blood flow during local knee-extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. Results, Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min,1·100 g,1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. Conclusions, Mild-to-moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity. [source] Cardiac and coronary function in the Langendorff-perfused mouse heart modelEXPERIMENTAL PHYSIOLOGY, Issue 1 2009Melissa E. Reichelt The Langendorff mouse heart model is widely employed in studies of myocardial function and responses to injury (e.g. ischaemia). Nonetheless, marked variability exists in its preparation and functional properties. We examined the impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca2+] and pacing rate on contractile function and responses to 20 min ischaemia followed by 45 min reperfusion. We also assessed the impact of strain, and tested the utility of the model in studying coronary function. Under normoxic conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate [Ca2+], 420 beats min,1) exhibited 145 ± 2 mmHg left ventricular developed pressure (LVDP). Force development declined by ,15% (126 ± 5 mmHg) with a reduction in free [Ca2+] to 1.35 mm, and by 25% (108 ± 3 mmHg) with increased pacing to 600 beats min,1. While elevated heart rate failed to modify ischaemic outcome, the lower [Ca2+] significantly improved contractile recovery (by >30%). We detected minimal sex-dependent differences in normoxic function between 8 and 24 weeks, although age modified contractile function in males (increased LVDP at 24 versus 8 weeks) but not females. Both male and female hearts exhibited age-related reductions in ischaemic tolerance, with a significant decline in recovery evident at 16 weeks in males and later, at 20,24 weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv, Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c hearts. In terms of vascular function, baseline coronary flow (20,25 ml min,1 g,1) was 50,60% of maximally dilated flows, and coronary reactive and functional hyperaemic responses were pronounced (up to 4-fold elevations in flow in hearts lacking ventricular balloons). These data indicate that attention to age (and sex) of mice will reduce variability in contractile function and ischaemic responses. Even small differences in perfusion fluid [Ca2+] also significantly modify tolerance to ischaemia (whereas modest shifts in heart rate do not impact). Ischaemic responses are additionally strain dependent, with BALB/c hearts displaying greatest intrinsic tolerance. Finally, the model is applicable to the study of vascular reactivity, providing large responses and excellent reproducibility. [source] Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitroFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2001Tijen Utkan Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol-fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium-dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats. [source] Trauma: physiology, pathophysiology, and clinical implicationsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2006DACVA, DACVECC, William Muir DVM Abstract Objective: To review the physiology, pathophysiology, and consequences of trauma. The therapeutic implications of hypovolemia, hypotension, hypothermia, tissue blood flow, oxygen delivery, and pain will be discussed. Data Sources: Human and veterinary clinical and research studies. Human and veterinary data synthesis: Trauma is defined as tissue injury that occurs more or less suddenly as a result of violence or accident and is responsible for initiating hyothalamic,pituitary,adrenal axis, immunologic and metabolic responses that are designed to restore homeostasis. Tissue injury, hemorrhage, pain, and fear are key components of any traumatic event. Trauma and blood loss result in centrally integrated autonomic-mediated cardiovascular responses that are designed to increase heart rate, systemic vascular resistance, and maintain arterial blood pressure (ABP) to vital organs at the expense of blood flow to the gut and skeletal muscle. Severe trauma elicits exuberant physiologic, immunologic, and metabolic changes predisposing the animal to organ malfunction, a systemic inflammatory response, infection, and multiple organ dysfunctions. The combination of both central and local influences produces regional redistribution of blood flow among and within tissue beds which, when combined with impaired vascular reactivity, leads to maldistribution of blood flow to tissues predisposing to tissue hypoperfusion and impaired oxygen delivery and extraction. Gut blood flow and viability may serve as a sentinel of patient survival. These consequences are magnified in animals suffering from pain or that become hypothermic. Successful treatment of traumatized animals goes beyond the restoration of blood pressure and urine output, is dependent on a fundamental understanding of the pathophysiologic processes responsible for the animals current physical status, and incorporates the reduction of pain, stress, and the systemic inflammatory response and methods that restore microcirculatory blood flow and tissue oxygenation. Conclusions: Severe trauma is a multifaceted event and is exacerbated by hypothermia, pain, and stress. Therapeutic approaches must go beyond the simple restoration of vascular volume and ABP by maintaining tissue blood flow, restoring tissue oxygenation, and preventing systemic inflammation. [source] Regulation of In Situ Skeletal Muscle Arteriolar Tone: Interactions Between Two ParametersMICROCIRCULATION, Issue 6 2002JEFFERSON C. FRISBEEArticle first published online: 26 JAN 2010 ABSTRACT Objective: The growing understanding of the complexity of mechanisms regulating arteriolar tone demands that a systematic determination of how these processes interact to alter diameter be undertaken. This study examined how five mediators of skeletal muscle distal arteriolar tone [adenosine concentration, oxygen content, ,-adrenergic activation (norepinephrine), intravascular pressure and wall shear rate], taken two parameters at a time, interact to regulate vessel diameter. Methods: The reactivity of distal arterioles of in situ rat cremaster muscle after alterations in each of the above mediators was assessed. In addition, arteriolar responses to all two-parameter combinations were evaluated to determine the effect of altered environment on vascular reactivity to stimuli. Results: Arteriolar dilation to adenosine was unaltered by changes in other parameters. In contrast, wall shear rate-induced arteriolar dilation was impaired by 60,88% after increases in the other parameters. Myogenic reactivity was reduced by 28% with elevated O2 and by 65% with norepinephrine (because of vessel closure) and was impaired by 89% with elevated adenosine. O2 -induced arteriolar reactivity was impaired by 56% with increased adenosine and by 44% with increased norepinephrine concentration but was largely unaffected by elevated intravascular pressure. Adrenergic reactivity was attenuated with elevated intravascular pressure (by 69%) and O2 (by 54%) because of vessel closure but was unaltered with elevated adenosine. Conclusions: These data suggest that (1) individual mediators contributing to the regulation of arteriolar tone exist within a hierarchy of importance and (2) mechanisms regulating arteriolar tone can be impacted by unidentified alterations in other processes. Ongoing investigation into interactions between multiple processes regulating arteriolar tone will allow for a more integrated understanding of how microvessels regulate their diameter. [source] Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in wistar ratsPHYTOTHERAPY RESEARCH, Issue 10 2009Roshan Tiwari Abstract The study aimed to evaluate the protective role of myricetin obtained from Vitis vinifera (Vitaceae) on heart rate, electrocardiographic (ECG) patterns, vascular reactivity to catecholamines, cardiac marker enzymes, antioxidant enzymes together with morphological and histopathological changes in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats. Rats treated with isoproterenol (85 mg/kg, administered subcutaneously twice at an interval of 24 h) showed a significant increase in heart rate and ST elevation in ECG, and a significant increase in the levels of cardiac marker enzymes , lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum. Isoproterenol significantly reduced superoxide dismutase (SOD) and catalase (CAT) activity and increased vascular reactivity to various catecholamines. Pretreatment with myricetin (100 mg/kg, p.o. and 300 mg/kg, p.o.) for a period of 21 days significantly inhibited the effects of ISO on heart rate, levels of LDH, CK, AST, SOD, CAT, vascular reactivity changes and ECG patterns. Treatment with myricetin (100 mg/kg and 300 mg/kg) alone did not alter any of the parameters compared with vehicle treated Wistar rats. Myricetin treated animals showed a lesser degree of cellular infiltration in histopathological studies. Thus, myricetin (100 mg/kg and 300 mg/kg) ameliorates the cardiotoxic effects of isoproterenol and may be of value in the treatment of MI. Copyright © 2009 John Wiley & Sons, Ltd. [source] The effect of a new topical local anaesthetic delivery system on forearm skin blood flow reactivity,ANAESTHESIA, Issue 2 2010M. D. Wiles Summary Different topical local anaesthetics have varying effects on skin blood flow and vascular reactivity. We compared the vasoactive properties of Rapydan®, a new topical local anaesthetic, with those of AmetopÔ and EMLAÔ creams in 20 healthy volunteers. Blood flow and vascular reactivity in the forearm skin were assessed by laser Doppler flowmetry and the transient hyperaemic response ratio respectively, before and after the application of EMLA (for 60 min), Ametop (for 30 and 60 min) and Rapydan (for 30 min). Application of EMLA had no effect on skin blood flow (median (IQR [range]) change from baseline ,0.9% (,63 to 414 [,38.5 to 51.3] %, p = 1.0)) or mean (SD) transient hyperaemic response ratio (from 2.86 (0.86) to 3.17 (1.3), p = 0.38). The application of Ametop for 60 min produced a greater median (IQR [range]) increase in blood flow from baseline (508 (,55 to 998 [148,649]) %) than Rapydan applied for 30 min 160 (,77 to 997 [45,301]) %, p = 0.001), and a similar decrease in mean (SD) transient hyperaemic response ratio (from 2.69 (1.16) to 1.08 (0.26) and from 2.83 (0.84) to 1.49 (0.93) respectively, p = 0.57). [source] Study of peripheral circulation in non-pregnant, pregnant and pre-eclamptic women using applied potential tomographyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2004Badreldeen AHMED Abstract Background:, Profound changes are known to occur in the cardiovascular system during pregnancy, involving an increase in cardiac output and a fall in peripheral resistance. In some women these adaptations may be inappropriate and this may result in pregnancy-induced hypertension and pre-eclampsia. Aims and methods:, The aims of the study were to evaluate the relatively new, non-invasive technique of applied potential tomography (APT) in measurements of peripheral blood flow, to study peripheral blood flow in a sample of non-pregnant, pregnant and pre-eclamptic women, and to investigate whether the adaptive changes in the peripheral circulation are different in pre-eclampsia compared with normal pregnancy. Applied potential tomography was used to assess peripheral vascular reactivity, by monitoring fluid distribution in calf muscles during postural change Results:, The APT technique was able to detect peripheral vasoconstriction in response to an increase in intramural pressure brought about by passive lowering of the leg (peripheral mechanisms). The peripheral vasoconstriction response was found to be more prominent in woman with pre-eclampsia. Conclusions:, The presence of a local reflex in the lower limb had been postulated and the effect of this reflex on the peripheral circulation could be detected using APT, regardless of how it was initiated. In normal pregnant women this reflex was diminished when compared to non-pregnant women, which might contribute to the reduction in peripheral vascular resistance seen in normal pregnancy. This reflex was defective in pre-eclampsia and this lack of adaptation may be a local reflex contributing to the raised peripheral resistance, which in turn may be a factor in high blood pressure in pre-eclampsia. [source] Inhibition of calcium/calmodulin-dependent protein kinase II normalizes diabetes-induced abnormal vascular reactivity in the rat perfused mesenteric vascular bedAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2003M. H. M. Yousif Summary 1 Calcium/calmodulin-dependent protein kinase II (CaMKII) has an important function in mediating insulin release but its role in the development of diabetes-induced cardiovascular complications is not known. 2 We investigated the ability of a chronic administration of KN-93 (5 mg kg,1alt diem for 4 weeks), an inhibitor of CaMKII, to modulate the altered vasoreactivity of the perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)-induced diabetes. 3 The vasoconstrictor responses induced by noradrenaline (NE), endothelin-1 (ET-1), and angiotensin II (Ang II), were significantly increased whereas, vasodilator responses to carbachol and histamine were significantly reduced in the perfused mesenteric bed of the STZ-diabetic rats as compared with non-diabetic controls. 4 Inhibition of CaMKII by KN-93 treatment did not affect blood glucose levels but produced a significant normalization of the altered agonist-induced vasoconstrictor and vasodilator responses. KN-93 did not affect agonist-induced responses in control animals. In addition, KN-93 significantly reduced weight loss in diabetic rats. 5 The present data suggest that CaMKII is an essential mediator in the development of diabetic vascular dysfunction and may also play an important role in signalling pathways leading to weight loss during diabetes. [source] Effects of lipopolysaccharide on vascular reactivity and mortality in ratsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 5-6 2002J. P. L. Nunes Summary 1 The effects of intraperitoneal (i.p.) lipopolysaccharide on vascular reactivity to noradrenaline in rat aorta under different conditions of passive tension, as well as on mortality in normotensive and hypertensive rats, were studied. 2 Concentration,response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g, from control and lipopolysaccharide-treated Wistar rats. Contractile responses were expressed as percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a resting tension of 2 g. The maxima were significantly larger (P < 0.05) at 3 g than at 0.5 g in both groups of rats: 117.8 vs. 62.3%, respectively, for control animals; 85.8 vs. 32.5%, respectively, for lipopolysaccharide-treated rats. 3 The 24-h mortality after the i.p. administration of lipopolysaccharide was lower in spontaneously hypertensive rats (1/12; 8%), when compared with control Wistar,Kyoto rats (5/11; 45%). However, mortality was higher in Wistar,Kyoto made hypertensive by 8-day administration of corticosterone (6/6; 100%). 4 We conclude that a differential sensitivity to noradrenaline of aortic smooth muscle at two different levels of passive tension is still present in lipopolysaccharide-treated animals. Chronic hypertension in SHR rats is associated with resistance to the lethal effects of lipopolysaccharide, whereas abrupt-onset hypertension induced by corticosterone leads to an increased mortality. 5 These results are compatible with the myofibrillary hypothesis, which explains vascular hyper-reactivity in chronic arterial hypertension, by postulating that a more favourable relative position (and/or proportion) for actin and myosin occurs, whereas in states of vascular hypo-reactivity, such as vasodilatory shock, the opposite phenomenon may exist. [source] Forearm blood flow in pre-eclampsiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2003Lucy Bowyer Objective 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and ,hCG) levels in the three groups of women. Design Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and NG -monomethyl- l -arginine (l -NMMA). Setting Research laboratory at St George Hospital, Kogarah, Sydney, Australia. Sample Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. Main outcome measures Changes in forearm blood flow in response to vasoactive substances. Results Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or l -NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. Conclusion The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to l -NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia. [source] Potential importance of alterations in hydrogen sulphide (H2S) bioavailability in diabetesBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2008D J Lefer Despite its long-standing reputation as a foul smelling and toxic gas that is associated with the decay of biological matter, hydrogen sulphide (H2S) has emerged as an important regulator of cardiovascular homoeostasis. H2S promotes a number of cellular signals that regulate metabolism, cardiac function and cell survival. Endogenous H2S bioavailability is regulated by several enzymes involved in the biosynthesis of cysteine. This study by Brancaleone et al. in the current issue of the British Journal of Pharmacology provides novel insights into the impairment of H2S biosynthesis in the setting of diabetes mellitus. The authors report that enzymic H2S biosynthesis is impaired in a murine model of type 1 diabetes and the attenuation in H2S bioavailability is associated with impaired vascular reactivity. This study has profound implications for the use of pharmacological agents to augment endogenous H2S synthesis or agents that release H2S to augment the levels of this gaseous signalling molecule in cardiovascular disease. British Journal of Pharmacology (2008) 155, 617,619; doi:fn1; published online 22 September 2008 [source] Effects of vitamin K1 supplementation on vascular responsiveness and oxidative stress in a rat femoral osteotomy modelCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2007Arda Tasatargil Abstract The main function of vitamin K1 is to act a co-factor for gamma-glutamyl carboxylase. However, it has also been shown to lessen oxidative stress. This study was aimed to evaluate the effect of vitamin K1 supplementation on vascular responsiveness and oxidative status in rats that underwent femoral osteotomy. Twenty-four male rats were divided into three groups to serve as sham, osteotomy and vitamin K1 groups. Indices of oxidative stress (catalase), and oxidative damage (malondialdehyde) were analysed in erythrocytes. In order to evaluate vascular reactivity, concentration-response curves to phenylephrine, angiotensin II, 5-hydroxytryptamine, bradykinin and histamine were constructed. The findings of this study clearly show that oxidative stress clearly increases after femoral osteotomy in rats. Also, this operation causes a significant depression in vascular responsiveness to contracting agents and endothelium-dependent vasodilators. However, vitamin K1 supplementation prevents vascular hyporeactivity by reducing oxidative stress and may represent a novel approach during osteotomy healing. Copyright © 2006 John Wiley & Sons, Ltd. [source] Phosphoinositide 3-kinase mediated signalling contributes to development of diabetes-induced abnormal vascular reactivity of rat carotid arteryCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2006Mariam H. M. Yousif Abstract Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive agents. Phosphatidylinositol 3-kinase (PI3K) is a signalling enzyme that plays key roles in vascular growth, proliferation and cellular apoptosis and is implicated in modulating vascular smooth muscle contractility. The aim of this study was to determine whether PI3K plays a role in development of diabetes-induced altered vascular reactivity to selected vasoconstrictors and vasodilators. The effect of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a selective PI3K inhibitor, on isolated segments of carotid arteries from streptozotocin (STZ)-diabetic rats was investigated. Ring segments of the isolated carotid arteries were mounted in organ baths to measure changes in isometric tension. Our results showed that STZ treatment produced an increase in the vasoconstrictor response to norepinephrine (NE), angiotensin II (Ang II) and endothelin-1 (ET-1) and an attenuated vasodilator response to carbachol and histamine in the isolated carotid arteries from STZ-diabetic animals. Diabetes-induced impaired vascular responsiveness to the vasoactive agonists was prevented by chronic inhibition of PI3K by LY294002 even though blood glucose levels remained high. This is the first study to show that selective inhibition of PI3K can attenuate the development of diabetes-induced abnormal vascular reactivity in the isolated carotid arteries of diabetic rats. Copyright © 2005 John Wiley & Sons, Ltd. [source] 2326: Influence of change in body position on choroidal blood flow in patients with obstructive sleep apnea syndromeACTA OPHTHALMOLOGICA, Issue 2010A ALMANJOUMI Purpose Obstructive sleep apnea syndrome (OSA) has been reported to be associated with ischemic and glaucomatous optic neuropathy (especially normal tension glaucoma). OSA per se is able to generate hypertension, atherosclerosis and autonomic dysfunction, all conditions possibly interacting with ocular vascular regulation. The aim of our study was to characterize the choroidal vascular reactivity to change in body position in OSA patients, as compared with matched healthy control subjects. Methods Eighteen newly diagnosed OSA patients were included in this prospective study. Control subjects were matched with OSA patients for body mass index (BMI), gender and age. At the screening visit, each subject underwent a general exam, cardiovascular, neurologic and ophthalmological examinations, and overnight polysomnography. The LDF instrument used in this study to measure subfoveal choroidal blood flow (ChBF), ChBVel , velocity (kHz); and volume, ChBVol (in arbitrary units, AU) Vascular choroidal reactivity was tested during the change in body position from the sitting to the supine position (10 min). Results OSA patients exhibited a similar choroidal reactivity during change in body position than controls with increased ChBVel (+15%), decreased ChBVol (-11.6%), and unchanged ChBF. IOP increased by 14.2% in the supine position whereas ocular perfusion pressure remained stable. Conclusion This prospective comparative study showed for the first time unimpaired choroidal vascular reactivity in otherwise healthy OSA patients. This suggests OSA patients, without comorbidities, has long-term adaptive mechanisms active in ocular microcirculation. [source] COMPARATIVE EFFECTS OF TRAMADOL ON VASCULAR REACTIVITY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008Juliana M Raimundo SUMMARY 1The aim of the present study was to determine the effects of tramadol on vascular reactivity in aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2Aortic rings, with or without endothelium, were obtained from male WKY rats and SHR (15,20 weeks old) and prepared for isometric tension recording. Aortic rings were precontracted with phenylephrine (10 µmol/L) or 40 mmol/L KCl and then exposed to cumulative concentrations of tramadol (0.1,1 mmol/L). 3Tramadol produced a concentration-dependent relaxation of precontracted aortic rings from WKY rats and SHR, which was not dependent on functional endothelium. Vascular relaxation was significantly greater in rings from SHR than WKY rats. 4The concentration of tramadol necessary to produce a 50% reduction of the maximal contraction to phenylephrine (IC50) in rings with and without endothelium from SHR was 0.47 ± 0.08 and 0.44 ± 0.03 mmol/L, respectively (P = 0.76). 5Tramadol attenuated the contracture elicited by Ca2+ in depolarized tissue, suggesting that it may inhibit L-type Ca2+ channels. However, pretreatment with nicardipine (1 µmol/L) prevented the relaxation induced by tramadol in aortic rings from WKY rats and partially reduced its inhibitory effect in aortic rings from SHR. 6Pretreatment of endothelium-denuded aorta with glybenclamide (3 µmol/L), 4-aminopyridine (3 mmol/L), tetraethylammonium (3 mmol/L) and naloxone (100 µmol/L) did not affect tramadol-induced vasodilation of aortic rings from either WKY rats or SHR. 7Intravenous administration of tramadol (10 mg/kg) to conscious SHR significantly reduced both systolic and diastolic blood pressure from 171.4 ± 5.3 to 129.3 ± 5.3 (P = 0.002) and from 125.0 ± 6.5 to 57.8 ± 8.9 mmHg (P = 0.003), respectively. [source] INVESTIGATION OF THE MICROCIRCULATION AND THE STATE OF OXIDATIVE STRESS IN THE RAT AFTER SCORPION ENVENOMATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2007Z Sahnoun SUMMARY 1Severe cases of scorpion envenomation (SE) generally show both respiratory and cardiocirculatory dysfunction. However, the pathophysiology of SE remains controversial. In the present study, we tried to explain the pathophysiology of the haemodynamic perturbations and cardiac failure in rats poisoned by the venom of Buthus occitanus tunetanus through a histomorphometric study of myocardial and muscular skeletal microcirculation and analysis of the oxidative stress state in order to evaluate the implication of the inflammatory process in the pathogenesis of SE. 2Experiments were performed on 96 rats divided into 16 groups (n = 6 in each group). Two groups were used to determine the optimum conditions of venom administration and times when to measure haemodynamic parameters. The B. occitanus tunetanus venom was administered at a dose of 800 µg/kg and tissues were removed 5 and 20 min after envenomation. Six groups were used for histomorphometric study: two control groups, two poisoned groups an two melatonin-pretreated and poisoned groups. The histomorphometric study was performed on isolated hearts and skeletal muscles. The final eight groups of rats (two control groups, two envenomated groups, two control groups pretreated with melatonin and two groups pretreated and envenomated) were used to investigate the state of tissue oxidative stress during SE and to evaluate the anti-oxidant effect of melatonin on rats poisoned with B. occitanus tunetanus venom. This study was based on the determination of tissue malondialdehyde in isolated organs as an indicator of thiobarbituric acid-reactive substances (TBARS). Melatonin was injected at a dose of 5 mg/kg, i.v., 15 min before the administration of serum or venom. Data were compared using analysis of variance and Tukey's test for multiple pair-wise comparisons. 3Five minutes after venom injection, a significant reduction in the mean relative volume of venules and arterioles in the heart and skeletal muscles of poisoned rats was noted. Twenty minutes after venom injection, these volumes were significantly increased in the heart and skeletal muscles of poisoned rats. Pretreatment of envenomated rats with melatonin resulted in a significant decrease in the mean relative volume of the venules and arterioles in the heart and skeletal muscles 5 and 20 min after venom injection compared with untreated envenomated rats. Investigation of the oxidative stress state showed a highly significant increase in TBARS in poisoned rats compared with control groups 5 and 20 min after venom injection. Melatonin pretreatment of rats poisoned with B. occitanus tunetanus venom resulted in an important and highly significant reduction of TBARS compared with untreated envenomated rats. 4It appears from the results of the present study that administration of B. occitanus tunetanus venom engendered an excessive myocardial and skeletal muscular vasoconstriction attributed to massive catecholamine release followed by arteriolar and venular vasodilatation. This venous stasis at the muscular microcirculation could be due to myocardiac failure. However, the concomitant presence of arteriolar vasodilatation suggests an inflammatory process in the pathophysiology of SE. This process was suggested by the genesis of a state of oxidative stress in relation to the important lipoperoxidation, which was inhibited by administration of the anti-oxidant melatonin. Thus, melatonin pretreatment seemed to accentuate the first phase of vascular reactivity in envenomed rats and inhibit the second vasodilator phase observed 20 min after administration of the venom. [source] DOSE-DEPENDENT EFFECT OF CAPTOPRIL ON AORTIC REACTIVITY OF STREPTOZOTOCIN-DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2004Tourandokht Baluchnejadmojarad Summary 1.,Diabetes mellitus is a primary risk factor for cardiovascular disorders. Strategies that interrupt the renin,angiotensin system have been known to reduce cardiovascular disease. The present study was performed to investigate the effect of sub-chronic administration of captopril on the aortic reactivity of streptozotocin-diabetic rats. 2.,Streptozotocin-diabetic rats received captopril (30 and 50 mg/kg per day) for 2 months. Contractile responses to phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and isosorbide dinitrate (ISD) were obtained from aortic rings. 3.,Concentration,response curves from captopril-treated diabetic rats to PE were attenuated compared with vehicle (Saline)-treated diabetic rats, especially at a dose of 50 mg/kg captopril. In addition, endothelium-dependent relaxation responses induced by ACh were significantly higher in captopril-treated diabetic rats compared with diabetic rats. The endothelium-independent relaxation responses for ISD were found not to be significantly different among the groups. 4.,Therefore, sub-chronic treatment of diabetic rats with captopril in a dose-dependent manner could prevent the functional changes in vascular reactivity in diabetic rats. [source] Redox-dependent signalling by angiotensin II and vascular remodelling in hypertensionCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Rhian M Touyz Summary 1.,Hypertension is associated with structural alterations of resistance arteries, a process known as remodelling (increased media-to-lumen ratio). 2.,At the cellular level, vascular remodelling involves changes in vascular smooth muscle cell (VSMC) growth, cell migration, inflammation and fibrosis. These processes are mediated via multiple factors, of which angiotensin (Ang) II appears to be one of the most important in hypertension. 3.,Angiotensin II signalling, via AT1 receptors, is upregulated in VSMC from resistance arteries of hypertensive patients and rats. This is associated with hyperactivation of vascular NADPH oxidase, leading to increased generation of reactive oxygen species (ROS), particularly O2, and H2O2. 4.,Reactive oxygen species function as important intracellular second messengers to activate many downstream signalling molecules, such as mitogen-activated protein kinase, protein tyrosine phosphatases, protein tyrosine kinases and transcription factors. Activation of these signalling cascades leads to VSMC growth and migration, modulation of endothelial function, expression of pro-inflammatory mediators and modification of extracellular matrix. 5.,Furthermore, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. 6.,All these processes play major roles in vascular injury associated with hypertension. Accordingly, ROS and the signalling pathways that they modulate provide new targets to regress vascular remodelling, reduce peripheral resistance and prevent hypertensive end-organ damage. 7.,In the present review, we discuss the role of ROS as second messengers in AngII signalling and focus on the implications of these events in the processes underlying vascular remodelling in hypertension. [source] Propofol differently alters vascular reactivity in normotensive and hypertensive ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2002Emmanuel Samain Summary 1.,The effect of propofol on arterial tone in hypertension is poorly understood. We examined the effect of increasing concentrations of propofol (5.6 × 10,8 to 2.8 × 10,3 mol/L) on isometric tension developed by noradrenaline (10,7 mol/L)-contracted aortic rings from 12-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2.,In both WKY rats and SHR, propofol induced a dose-dependent inhibition of contraction induced by noradrenaline, but the amplitude of relaxation was larger in the SHR than in WKY rats. 3.,The effects of propofol was endothelium independent in WKY rats, whereas in SHR relaxation induced by propofol was greater in endothelium-intact than in endothelium-denuded rings. 4.,In conclusion, we found significant differences in the effect of propofol in hypertensive rats, which may be related to differences in structural and functional properties of the arterial wall observed in hypertension. [source] Growth hormone, acromegaly, and heart failure: an intricate triangulationCLINICAL ENDOCRINOLOGY, Issue 6 2003Luigi Saccà Summary Short-term GH or IGF-I excess provides a model of physiological cardiac growth associated with functional advantage. The physiological nature of cardiac growth is accounted for by the following: (i) the increment in cardiomyocyte size occurs prevalently at expense of the short axis. This is the basis for the concentric pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall stress and functional improvement; (ii) cardiomyocyte growth is associated with improved contractility and relaxation, and a favourable energetic setting; (iii) the capillary density of the myocardial tissue is not affected; (iv) there is a balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not perturbed; and (vi) the growth response is not associated with the gene re-programming that characterizes pathologic cardiac hypertrophy and heart failure. Overall, the mechanisms activated by GH or IGF-I appear to be entirely different from those of chronic heart failure. Not to be neglected is also the fact that GH, through its nitric oxide (NO)-releasing action, contributes to the maintenance of normal vascular reactivity and peripheral vascular resistance. This particular kind of interaction of GH with the cardiovascular system accounts for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the beneficial effects of GH and IGF-I in various models of heart failure; (iii) the protective effect of GH and IGF-I against post-infarction ventricular remodelling; (iv) the reversal of endothelial dysfunction in patients with heart failure treated with GH; and (v) the cardiac abnormalities associated with GH deficiency and their correction after GH therapy. If it is clear that GH and IGF-I exert favourable effects on the heart in the short term, it is equally undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if it is not corrected, eventually leads to cardiac failure. Why then, at one point in time in the natural history of acromegaly, does physiological cardiac growth become maladaptive and translate into heart failure? Before this transition takes places, the acromegalic heart shares very few features with other models of chronic heart failure. None of the mechanisms involved in the progression of heart failure is clearly operative in acromegaly, save for the presence of insulin-resistance and mild alterations of lipoproteins and clot factors. Is this enough to account for the development of heart failure? Probably not. On the other hand, it must be stressed that GH and IGF-I activate several mechanisms that play a protective role against the development of heart failure. These include ventricular unloading, deactivation of neurohormonal components, antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data available concur to hypothesize that acromegalic cardiomyopathy represents a progressive model of cardiac hypertrophy in which the cardiotoxic and pro-remodelling effect is intrinsic to the excessive and unrestrained myocardial growth. [source] Forearm blood flow measurements using computerized R-wave triggered strain-gauge venous occlusion plethysmography: unilateral vs. bilateral measurementsCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 5 2001Adriaan M. Kamper The human forearm is a well established model to study local vascular reactivity in humans in vivo, using strain-gauge venous occlusion plethysmography to measure blood flow and changes in blood flow in the forearm. To reduce the intra-individual variability of the forearm blood flow (FBF), it has been advocated that simultaneous measurements of contralateral forearm blood flow is obligatory. Therefore, the use of the calculated forearm ratio (FR) is recommended instead of using the actual FBF. In the present study we compared the intra-individual variability of forearm blood flow measurements and the forearm ratio, by using computerized R-wave triggered strain-gauge venous occlusion plethysmography, to test if bilateral expression of measurements is better than unilateral. Results were obtained in eight volunteers. Intra-arterial infused sodium nitroprusside induced a dose dependent increase in forearm blood flow and a dose dependent increase in the calculated forearm ratio. Intra-arterial infused norepinephrine induced a dose dependent decrease in forearm blood flow and a dose dependent decrease in the calculated forearm ratio. The differences between the variation coefficients of the forearm blood flow measurements and the calculated forearm ratio were different. These results support our hypothesis that by using a computerized, R-wave triggered system for unilateral forearm blood flow measurement is a more reliable outcome than the calculated forearm ratio derived from bilateral measurements. [source] | ||||||||||||||||||||||||||||