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Vascular Conductance (vascular + conductance)

Distribution by Scientific Domains

Life Sciences	61%
Medical Sciences	38%

Selected Abstracts

The acute effects of smokeless tobacco (snuff) on gingival blood flow in man

JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2001
Antonios Mavropoulos
Snuff-induced blood flow responses in the gingiva were evaluated in 22 healthy casual consumers of tobacco. Laser Doppler flowmetry (LDF) was used to measure blood flow simultaneously and continuously on two gingival sites (buccal aspect of the papillae between the upper lateral incisors and canines). In addition, measurements of skin blood flow in the forehead and palmar side of the left thumb were performed. Arterial blood pressure (BP) and heart rate (HR) were also recorded. Unilateral application of commercial snuff (500 mg, 1%) caused a marked and rapid increase in gingival blood flow (GBF) on the exposed side (p<0.001). Blood flow increased also in the contralateral gingiva and forehead skin (p<0.05). Skin blood flow in the thumb showed an insignificant decrease. BP and HR increased. Vascular conductance increased significantly in the snuff-exposed gingiva but not in the contralateral gingiva or the forehead. Vascular conductance was largely unaffected in the thumb. It is concluded that acute application of snuff, besides giving rise to typical changes in BP and HR, increases GBF in and around the exposed area, probably through activation of sensory nerves and the subsequent release of vasodilatory peptides from their peripheral endings. Blood flow in unexposed gingival and forehead skin may increase probably due to humoral or nervously mediated mechanisms. However, a passive pressure-induced hyperaemia in the unexposed gingiva and forehead skin can not be excluded. [source]

Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pig

ACTA PHYSIOLOGICA, Issue 1 2002
R. J. M. Middelveld
ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source]

Forearm vascular responses to combined muscle metaboreceptor activation in the upper and lower limbs in humans

EXPERIMENTAL PHYSIOLOGY, Issue 4 2006
Ken Tokizawa
Our previous studies showed that venous occlusion or passive stretch of the lower limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non-exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb. In this study, we investigated whether a metabolic stimulus to the lower limb induces a similar response. Eight subjects performed a 2 min static handgrip exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30% MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non-exercised arm decreased significantly, whereas during combined PEMI of the upper and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb was attenuated. Forearm blood flow and FVC were significantly greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. When PEMI of the lower limb was released after combined PEMI of the upper and lower limbs (only PEMI of the upper limb was maintained continuously), the attenuated decreases in FBF and FVC observed during combined PEMI of the upper and lower limbs was not observed. Thus, forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs. [source]

Recent Insights into Carotid Baroreflex Function in Humans Using the Variable Pressure Neck Chamber

EXPERIMENTAL PHYSIOLOGY, Issue 6 2003
Paul J. Fadel
The variable pressure neck chamber has provided an invaluable research tool for the non-invasive assessment of carotid baroreflex (CBR) function in human investigations. The ability to construct complete stimulus-response curves and define specific parameters of the reflex function curve permits statistical comparisons of baroreflex function between different experimental conditions, such as rest and exercise. Results have convincingly indicated that the CBR stimulus-response curve is reset during exercise in an intensity-dependent manner to functionally operate around the prevailing pressure elicited by the exercise workload. Furthermore, both at rest and during exercise, alterations in stroke volume do not contribute importantly to the maintenance of arterial blood pressure by the carotid baroreceptors, and therefore, any reflex-induced changes in cardiac output (Q) are the result of CBR-mediated changes in heart rate. However, more importantly, the CBR-induced changes in mean arterial pressure (MAP) are primarily mediated by alterations in vascular conductance with only minimal contributions from Q to the initial reflex MAP response. Thus, the capacity of the CBR to regulate blood pressure depends critically on its ability to alter vascular tone both at rest and during exercise. This review will emphasize the utility of the variable pressure neck chamber to assess CBR function in human experimental investigations and the mechanisms by which the CBR responds to alterations in arterial blood pressure both at rest and during exercise. [source]

Measurement of Muscle Microvascular Oxygen Pressures: Compartmentalization of Phosphorescent Probe

MICROCIRCULATION, Issue 4 2004
DAVID C. POOLE
Objective: To determine whether the phosphorescent probe Oxyphor R2 (a palladium porphyrin dendrimer) becomes extravasated within normotensive skeletal muscle, R2 perfusion and washout studies were performed using a perfused rat hindlimb preparation. Methods: Phosphorescence signals were monitored in tibialis anterior muscles after 35 min of R2 blood perfusion and across a subsequent washout period that included vasodilation (sodium nitroprusside, SNP, ,3 × 10,2 M). Results: Two responses were evident: Group 1 (n = 4),Inflowing blood pressure and vascular conductance remained stable close to initial values and subsequently a marked vasodilation was evident with SNP (vascular conductance; R2 blood perfusion, 0.096 ± 0.005; washout, pre-SNP, 0.085 ± 0.005, post-SNP, 0.110 ± 0.005 mL/min/mmHg, p < .05, for pre- vs. post-SNP). Baseline phosphorescence signals could be monitored up to 99 ± 36 s post-SNP when the phosphorescence signal disappeared. For these muscles, palladium content was undetectable. Group 2 (n = 3),Inflowing blood pressure increased 112% and vascular conductance fell , 50%. These hindlimbs were unresponsive to SNP, phosphorescence signal was undiminished by washout and SNP, and muscles became edematous. Conclusions: These results suggest that in normotensive muscle (i.e., Group 1 above), extravasation of phosphorescent probe R2 over 35 min of perfusion is insufficient to yield a detectable phosphorescence signal in skeletal muscle. [source]

,-Adrenergic and neuropeptide Y Y1 receptor control of collateral circuit conductance: influence of exercise training

THE JOURNAL OF PHYSIOLOGY, Issue 24 2008
Jessica C. Taylor
This study evaluated the role of ,-adrenergic receptor- and neuropeptide Y (NPY) Y1 receptor-mediated vasoconstriction in the collateral circuit of the hind limb. Animals were evaluated either the same day (Acute) or 3 weeks following occlusion of the femoral artery; the 3-week animals were in turn limited to cage activity (Sed) or given daily exercise (Trained). Collateral-dependent blood flows (BFs) were measured during exercise with microspheres before and after ,-receptor inhibition (phentolamine) and then NPY Y1 receptor inhibition (BIBP 3226) at the same running speed. Blood pressures (BPs) were measured above (caudal artery) and below (distal femoral artery) the collateral circuit. Arterial BPs were reduced by ,-inhibition (50,60 mmHg) to ,75 mmHg, but not further by NPY Y1 receptor inhibition. Effective experimental sympatholysis was verified by 50,100% increases (P < 0.001) in conductance of active muscles not affected by femoral occlusion with receptor inhibition. In the absence of receptor inhibition, vascular conductance of the collateral circuit was minimal in the Acute group (0.13 ± 0.02), increased over time in the Sed group (0.41 ± 0.03; P < 0.001), and increased further in the Trained group (0.53 ± 0.03; P < 0.02). Combined receptor inhibition increased collateral circuit conductances (P < 0.005), most in the Acute group (116 ± 37%; P < 0.02), as compared to the Sed (41 ± 6.6%; P < 0.001) and Trained (31 ± 5.6%; P < 0.001) groups. Thus, while the sympathetic influence of the collateral circuit remained in the Sed and Trained animals, it became less influential with time post-occlusion. Collateral conductances were collectively greater (P < 0.01) in the Trained as compared to Sed group, irrespective of the presence or absence of receptor inhibition. Conductances of the active ischaemic calf muscle, with combined receptor inhibition, were suboptimal in the Acute group, but increased in Sed and Trained animals to exceptionally high values (e.g. red fibre section of the gastrocnemius: ,7 ml min,1 (100 g),1 mmHg,1). Thus, occlusion of the femoral artery promulgated vascular adaptations, even in vessels that are not part of the collateral circuit. The presence of active sympathetic control of the collateral circuit, even with exercise training, raises the potential for reductions in collateral BF below that possible by the structure of the collateral circuit. However, even with release of this sympathetic vasoconstriction, conductance of the collateral circuit was significantly greater with exercise training, probably due to the network of structurally larger collateral vessels. [source]

Exercise prevents age-related decline in nitric-oxide-mediated vasodilator function in cutaneous microvessels

THE JOURNAL OF PHYSIOLOGY, Issue 14 2008
Mark A. Black
Ageing is associated with impaired endothelium-derived nitric oxide (NO) function in human microvessels. We investigated the impact of cardiorespiratory fitness and exercise training on physiological and pharmacological NO-mediated microvascular responses in older subjects. NO-mediated vasodilatation was examined in young, older sedentary and older fit subjects who had two microdialysis fibres embedded into the skin on the ventral aspect of the forearm and laser Doppler probes placed over these sites. Both sites were then heated to 42°C, with Ringer solution infused in one probe and N -nitro- l -arginine methyl ester (l -NAME) through the second. In another study, three doses of ACh were infused in the presence or absence of l -NAME in similar subjects. The older sedentary subjects then undertook exercise training, with repeat studies at 12 and 24 weeks. The NO component of the heat-induced rise in cutaneous vascular conductance (CVC) was diminished in the older sedentary subjects after 30 min of prolonged heating at 42°C (26.9 ± 3.9%CVCmax), compared to older fit (46.2 ± 7.0%CVCmax, P < 0.05) and young subjects (41.2 ± 5.2%CVCmax, P < 0.05), whereas exercise training in the older sedentary group enhanced NO-vasodilator function in response to incremental heating (P < 0.05). Similarly, the NO contribution to ACh responses was impaired in the older sedentary versus older fit subjects (low dose 3.2 ± 1.3 versus 6.6 ± 1.3%CVCmax; mid dose 11.4 ± 2.4 versus 21.6 ± 4.5%CVCmax; high dose 35.2 ± 6.0 versus 52.6 ± 7.9%CVCmax, P < 0.05) and training reversed this (12 weeks: 13.7 ± 3.6, 28.9 ± 5.3, 56.1 ± 3.9%CVCmax, P < 0.05). These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents age-related decline in indices of physiological and pharmacological microvascular NO-mediated vasodilator function. Since higher levels of NO confer anti-atherogenic benefit, this study has potential implications for the prevention of microvascular dysfunction in humans. [source]

During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level

THE JOURNAL OF PHYSIOLOGY, Issue 1 2008
Carsten Lundby
To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O2 delivery with O2 demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 ,g (kg body mass),1 min,1) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 ± 1.0 versus 7.9 ± 1.0 l min,1) and femoral arterial oxygen delivery (1.2 ± 0.2 versus 1.3 ± 0.2 l min,1; control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 ± 14.2 versus 83.3 ± 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 ± 5.3 to 72.0 ± 10.2% (P < 0.05), and the corresponding venous O2 content was increased from 25.5 ± 10.0 to 46.3 ± 18.5 ml l,1 (control and ATP, respectively, P < 0.05). With ATP, leg arterial,venous O2 difference was decreased (P < 0.05) from 139.3 ± 9.0 to 116.9 ± 8.4,1 and leg was 20% lower compared to the control trial (1.1 ± 0.2 versus 0.9 ± 0.1 l min,1) (P= 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O2 delivery with O2 demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg is not limited by restricted vasodilatation in the altitude-acclimatized human. [source]

Neurokinin-1 receptor desensitization to consecutive microdialysis infusions of substance P in human skin

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Brett 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]

Central command and the cutaneous vascular response to isometric exercise in heated humans

THE JOURNAL OF PHYSIOLOGY, Issue 2 2005
Manabu Shibasaki
Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature ,1°C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by ,12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0 ± 9.8 versus 18.6 ± 6.4 mmHg, P < 0.01), while the elevation of heart rate tended to be lower (19.4 ± 10.4 versus 27.4 ± 8.1 b.p.m., P= 0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans. [source]

Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skin

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
Lacy 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]

Reductions in basal limb blood flow and vascular conductance with human ageing: role for augmented ,-adrenergic vasoconstriction

THE JOURNAL OF PHYSIOLOGY, Issue 3 2001
Frank A. Dinenno
1Basal whole-limb blood flow and vascular conductance decrease with age in men. We determined whether these age-associated changes in limb haemodynamics are mediated by tonically augmented sympathetic ,-adrenergic vasoconstriction. 2Seven young (28 ± 2 years; mean ±s.e.m.) and eight older (64 ± 2 years) healthy, normotensive adult men were studied. Baseline femoral artery blood flow (Doppler ultrasound) and calculated vascular conductance were 29 and 31 % lower, respectively, and vascular resistance was 53 % higher in the older men (all P < 0.001). 3Local (intra-femoral artery) ,-adrenergic receptor blockade with phentolamine evoked greater increases in femoral blood flow (105 ± 11 vs. 60 ± 6 %) and vascular conductance (125 ± 13 vs. 66 ± 7 %), and reductions in vascular resistance (55 ± 2 vs. 39 ± 3 %) in the experimental limb of the older compared with the young men (all P < 0.001). As a result, ,-adrenergic receptor blockade eliminated the significance of the age-associated differences in absolute levels of femoral blood flow (500 ± 51 vs. 551 ± 35 ml min,1), vascular conductance (6.02 ± 0.73 vs. 6.33 ± 0.26 U), and vascular resistance (0.17 ± 0.03 vs. 0.16 ± 0.01 U; P= 0.4,0.8, n.s.). Femoral haemodynamics in the control limb were unaffected by phentolamine administration in the contralateral (experimental) limb. Complete ,-adrenergic receptor blockade was demonstrated by the absence of vasoconstriction in the experimental limb in response to the cold pressor test. Local propranolol was administered to control for any ,-adrenergic effects of phentolamine. Propranolol did not affect haemodynamics in the experimental or control limbs. 4Our results indicate that the age-related reductions in basal limb blood flow and vascular conductance are mediated largely by chronically elevated sympathetic ,-adrenergic vasoconstriction. This may have important physiological and pathophysiological implications for the ageing human. [source]

Regional haemodynamic effects of cyclosporine A, tacrolimus and sirolimus in conscious rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2004
S M Gardiner
The observation that the immunosuppressants, cyclosporine A (CsA) and tacrolimus, have pressor effects, but sirolimus does not, has led to an hypothesis that generalised sympathoexcitation, resulting from inhibition of calcineurin by CsA and tacrolimus underlies their pressor effects, because sirolimus does not inhibit calcineurin. It is unknown if sirolimus has haemodynamic actions not accompanied by a pressor effect, and whether or not the pressor effects of CsA and tacrolimus are accompanied by similar haemodynamic changes. Therefore, the first aim of our studies was to investigate these possibilities in conscious, chronically-instrumented, male, Sprague-Dawley rats. CsA (5.9 mg kg,1 bolus i.v.) caused rapid-onset, prolonged hypertension, tachycardia and mesenteric vasoconstriction. There was a slower onset renal vasoconstriction, but no significant change in hindquarters vascular conductance; all the effects of CsA were significantly greater than those of vehicle. CsA given by infusion (over 30 min or 2 h) caused changes qualitatively similar to those above. Repeated administration of CsA over 4 days did not enhance its cardiovascular effects. Pretreatment with the angiotensin (AT1) receptor antagonist, losartan, and the endothelin (ETA and ETB) receptor antagonist, SB 209670, reduced the pressor and mesenteric vasoconstrictor effects of CsA. Additional administration of the , -adrenoceptor antagonist, phentolamine, completely inhibited the cardiovascular effects of CsA. Tacrolimus (450 ,g kg,1 bolus i.v.) caused similar peak pressor and tachycardic effects to CsA, but these were much slower in onset, and were maximal when there were no significant regional vasoconstrictions, indicating that the pressor effect was probably due to a rise in cardiac output. However, although propranolol reversed the tachycardic effect of tacrolimus, it did not influence the pressor response. Sirolimus (450 ,g kg,1 bolus i.v.) had no tachycardic action, and only a modest, transient pressor effect, accompanied by equally brief reductions in renal, mesenteric, and hindquarters vascular conductances. The differences between the regional haemodynamic profiles of equipressor doses of CsA and tacrolimus, and the finding that sirolimus has significant cardiovascular actions, indicate that generalised sympathoexcitation, resulting from calcineurin inhibition (with CsA and tacrolimus), is unlikely to be the sole explanation of their pressor effects. British Journal of Pharmacology (2004) 141, 634,643. doi:10.1038/sj.bjp.0705659 [source]

Cardiovascular reflex responses after intrathecal ,-conotoxins or dexmedetomidine in the rabbit

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2003
Duncan W Blake
Summary 1.,The effects of thoracic intrathecal doses (1 µg/kg) of the ,2 -adrenoceptor agonist dexmedetomidine and ,-conotoxins MVIIA and CVID on vasoconstrictor and heart rate responses to acute central hypovolaemia were studied in seven chronically instrumented rabbits. 2.,Gradual inflation of an inferior vena cava cuff to reduce cardiac index (CI) by 8% per minute induced progressive vasoconstriction and an increase in heart rate (phase I). At approximately 40% of resting CI, there was sudden decompensation with failure of vasoconstriction and decrease in mean arterial pressure (MAP; phase II). 3.,Both intrathecal MVIIA and CVID decreased resting CI (by 20% at 3 h), but only MVIIA significantly reduced resting MAP (P = 0.003). Dexmedetomidine resulted in transient bradycardia, but no other significant change in the resting circulation. With simulated haemorrhage, the relationship between CI and vascular conductance was shifted after MVIIA (1,3 h after injection) so that there was less vasoconstriction and a reduced increase in heart rate by the end of phase I compared with other treatments (P = 0.002 and P = 0.009, respectively). One hour after injection, dexmedetomidine reduced the slope of the phase I vasoconstrictor response (P = 0.03), but did not significantly alter the end-point of the response. With failure of vasoconstriction and the onset of phase II, vascular conductance was higher after MVIIA compared with controls. Both conotoxins caused progressive failure of vasoconstriction rather than recovery during phase II (P < 0.001). 4.,Intrathecal injections of these drugs to control chronic pain may compromise cardiovascular responses to changes in central blood volume. At the single doses studied, there were significant differences between the responses to simulated haemorrhage after MVIIA or dexmedetomidine compared with CVID, with the prolonged effect after MVIIA most likely to be of clinical significance. [source]

Effects of resistance training on cardiovascular responses to lower body negative pressure in the elderly

CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 5 2001
Lynn B. Panton
The purpose of the present study was to determine whether resistance training alters the cardiovascular responses to submaximal lower body negative pressure (LBNP) in the elderly. Twenty-one subjects were randomized into a control (C: n=10; 70 ± 3 years, mean ± SD) or a resistance training (TR: n=11; 67 ± 7 years) group. Subjects in the TR underwent 12 weeks of training consisting of three sets of 8,12 contractions at ,60,80% of their initial maximal one repetition, three times per week, on 10 different machines. Before (Pre) and after (Post) training, all subjects underwent exposures of LBNP of ,10, ,20 and ,40 Torr and muscle biopsy sampling at the vastus lateralis. TR increased (P,0·05) knee extension (Pre=379 ± 140 N, Post=534 ± 182 N) and chest press (Pre=349 ± 137 N, Post=480 ± 192 N) strength. Neither body weight nor percentage body fat were altered (P,>0·05) by training. Resistance training increased (P,0·05) cross-sectional area in both Type I (4203 ± 1196 to 5248 ± 1728 ,m2) and Type II (3375 ± 1027 to 4286 ± 1892 ,m2) muscle fibres. Forearm blood flow, forearm vascular conductance, mean arterial pressure, and heart-rate responses to LBNP were not altered by the training. These data suggest that the cardiovascular responses of elderly to LBNP are unaffected by 12 weeks of whole-body resistance training despite increases in muscle strength and size. [source]

Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009
W-S Vanessa Ho
Background and purpose:, The cardiovascular effects of cannabinoids can be influenced by anaesthesia and can differ in chronic hypertension, but the extent to which they are influenced by acute hypertension in conscious animals has not been determined. Experimental approach:, We examined cardiovascular responses to intravenous administration of anandamide and the synthetic cannabinoid, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55212-2), in conscious male Wistar rats made acutely hypertensive by infusion of angiotensin II (AII) and arginine vasopressin (AVP). Rats were chronically instrumented for measurement of arterial blood pressure and vascular conductances in the renal, mesenteric and hindquarters beds. Key results:, Anandamide dose-dependently decreased the mean arterial blood pressure of rats made hypertensive by AII-AVP infusion, but not normotensive rats. Interestingly, acute hypertension also revealed a hypotensive response to WIN55212-2, which caused hypertension in normotensive animals. The enhanced depressor effects of the cannabinoids in acute hypertension were associated with increased vasodilatation in hindquarters, renal and mesenteric vascular beds. Treatment with URB597, which inhibits anandamide degradation by fatty acid amide hydrolase, potentiated the depressor and mesenteric vasodilator responses to anandamide. Furthermore, haemodynamic responses to WIN55212-2, but not to anandamide, were attenuated by the CB1 receptor antagonist, AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide]. Conclusions and implications:, These results broadly support the literature showing that the cardiovascular effects of cannabinoids can be exaggerated in hypertension, but highlight the involvement of non-CB1 receptor-mediated mechanisms in the actions of anandamide. [source]