Mesenteric Vascular Conductance Research Articles

Effects of chronic infusions of alpha-trinositol on regional and cardiac haemodynamics in conscious rats.

1. Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-1, n = 8) or alpha-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg-1 h-1 (0.3 ml h-1; n = 9). During infusion of alpha-trinositol at 5 or 20 mg kg-1 h-1, cardiovascular changes were little different from those seen during saline infusion. However, during infusion of alpha-trinositol at 80 mg kg-1 h-1 there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different from the changes seen in the saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2. Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h-1) or alpha-trinositol (2 mg kg-1 bolus, 80 mg kg-1 h-1 infusion at 0.3 ml h-1). During the infusion of saline, there were slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving alpha-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3. These results, collectively, indicate that incremental infusions of alpha-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms. However, infusion of alpha-trinositol at a high dose causes substantial increases in renal,mesenteric and hindquarters flows and vascular conductances, supported by significant increases in indices of cardiac inotropism. Such effects, in the absence of significant hypotension, tachycardia or signs of desensitization, give alpha-trinositol a unique cardiovascular profile.

Cardiovascular effects of neuronal activation of the extended amygdala in rats

The bed nucleus of the stria terminalis (BST) and the sublenticular substantia innominata (SI) are considered rostral extensions of the medial and central amygdaloid nuclei. In contrast to amygdaloid nuclei proper, the involvement of BST and SI neurons in cardiovascular control has not been studied. These areas were systematically explored in 35 urethane-anesthetized Wistar rats for sites from which changes in arterial pressure (AP) and heart rate (HR) could be obtained by injection of 20 nl of glutamate solutions (Glu, 0.5 M). Injections into 84 of the 130 histologically verified sites were followed after an8.0±0.7 s latency by depressor responses ranging from −4 to −33 (mean−13.3±0.8) mmHg, accompanied by variable changes in HR. Pressor responses were elicited from only 3 sites; 43 sites were not responsive. An additional group of 10 rats was instrumented for bilateral Glu injections (0.1 M, 200 nl per side) into the ventral division of the lateral BST and ventral BST and for the recording of AP, HR and regional blood flows measured with pulsed Doppler probes in the conscious state. In these rats, decreases in AP (−11.9±1.7mmHg) were accompanied by significant increases in hinquarter conductance (44.2±11.45), while renal and mesenteric vascular conductances remained unchanged. The fall in AP usually preceded the rise in hindquarer flow. These results suggest the existence of a depressor area in regions of the BST and SI, but the contribution of the elicited depressor effects in the overall central control of the circulation remains to be established.

Regional haemodynamic effects of angiotensin II (3-8) in conscious rats.

1. It has been reported that angiotensin II (AII) (3-8) causes endothelium-dependent renal cortical vasodilatation, in anaesthetized rats, through interaction with a novel receptor that shows no affinity for the AT1-receptor antagonist, losartan. Therefore in order to get a fuller profile of the regional haemodynamic effects of AII (3-8) in conscious rats we assessed its renal, mesenteric and hindquarters vascular effects, and compared them to the responses elicited by AII and AIII. 2. AII and AIII (1.25, 12.5 and 125 pmol kg-1) caused dose-dependent pressor and renal and mesenteric vasoconstrictor effects. At doses up to 125 pmol kg-1, AII (3-8) was without any cardiovascular effects, but with doses of 1.25 and 12.5 nmol kg-1 there were dose-dependent increases in mean arterial blood pressure and reductions in renal and mesenteric flows and vascular conductances. The responses to AII (3-8) (12.5 nmol kg-1) were abolished by losartan (20 mumol kg-1). 3. Since it has been found that pretreatment with L-arginine can reveal a vasodilator effect of AII (3-8) on rabbit pial arterioles, we assessed responses to AII (3-8) (12.5 nmol kg-1) before and 5 min after onset of a primed infusion of L-arginine (1.4 mmol kg-1 bolus, 1.4 mmol kg-1 h-1 infusion). Responses to AII (3-8) were unchanged by L-arginine. 4. The results are consistent with AII (3-8) being a less effective agonist than All (or AIII) at the AT1-receptor, but provide no evidence for AII (3-8) interacting with a novel receptor that shows no affinity for losartan.

Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: Possible mechanisms of action

The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01–10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hindquarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, α-adrenoceptor-mediated constriction in the mesenteric vascular bed and β-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V 1-receptor antagonist, d(CH 2) 5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the paraventricular nuclei were abolished, as were the vasoconstrictions in the renal, superior mesenteric and hindquarter vascular beds. Together these results suggest an interaction between the sympathoadrenal system and vasopressin-mediated mechanisms in the cardiovascular responses to noradrenaline injected bilaterally into the paraventricular nuclei of conscious, untreated rats.

Involvement of capsaicin-sensitive neurones in the haemodynamic effects of exogenous vasoactive peptides: studies in conscious, adult Long Evans rats treated neonatally with capsaicin.

1. The regional haemodynamic effects of i.v. bolus injections of bradykinin (0.05 or 0.5 nmol), cholecystokinin (0.175 or 1.75 nmol), substance P (0.01 or 0.1 nmol) and calcitonin gene-related peptide (0.05 or 0.5 nmol) were assessed in conscious, adult Long Evans rats that had been treated neonatally with either capsaicin (50 mg kg-1, s.c.) or vehicle. 2. In vehicle-treated rats, both doses of bradykinin were without effect on blood pressure, but caused tachycardia and hindquarters vasodilatation. Moreover, after the higher dose there were dilatations in the renal and superior mesenteric vascular beds. In capsaicin-treated rats the hindquarters vasodilator effects elicited by both doses of bradykinin were significantly reduced, while the tachycardia and responses in the renal and superior mesenteric vascular beds were unchanged. 3. In vehicle-treated rats, cholecystokinin caused dose-dependent increases in blood pressure accompanied by renal, superior mesenteric and hindquarters vasoconstriction followed, after the higher dose, by a hindquarters vasodilatation. The lower dose produced a tachycardia, while there was a bradycardia followed by a tachycardia after the higher dose. In capsaicin-treated rats, the pressor response, as well as the renal vasoconstrictor effects of cholecystokinin, were greater than in vehicle-treated rats, while the heart rate, superior mesenteric or hindquarters responses were not different. 4. In vehicle-treated rats, substance P produced a dose-dependent depressor response and tachycardia accompanied by dilatations in the renal and hindquarters vascular beds and constriction in the superior mesenteric vascular bed. In capsaicin-treated rats, the responses to the lower dose of substance P were not different from those in vehicle-treated rats, while the depressor response to the higher dose of substance P was slightly less than in vehicle-treated rats and the renal vasodilatation was absent.5. In vehicle-treated rats, calcitonin gene-related peptide caused dose-dependent hypotensive and tachycardic effects associated with dilatations in renal and hindquarters vascular beds and a constriction in the superior mesenteric vascular bed. After the higher dose, the renal vasodilatation was followed by a modest vasoconstriction. In capsaicin-treated rats, the depressor responses to both doses of calcitonin generelated peptide were slightly more prolonged than in vehicle-treated animals, whereas the heart rate and renal and mesenteric vascular conductance changes were not significantly different. However, there was a more sustained hindquarters vasodilator response to the higher dose of calcitonin gene-related peptide in the capsaicin-treated rats.6. The results suggest that peripheral, capsaicin-sensitive neurones are involved in the cardiovascular responses to exogenous bradykinin and cholecystokinin in conscious rats. It does not appear that the extent of involvement of these neurones is underestimated on account of development of marked supersensitivity to the peptides they normally release, since responses to such peptides (e.g. substance P and calcitonin gene-related peptide) are relatively normal in capsaicin-treated rats.

Effects of NG‐nitro‐l‐arginine methyl ester on vasodilator responses to adrenaline or BRL 38227 in conscious rats

1. Conscious, Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, were used to assess responses to 3 min infusions of the potassium channel opener, BRL 38227 (1 and 10 micrograms kg-1 min-1) or adrenaline (0.05 and 0.5 microgram kg-1 min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 3 mg kg-1 h-1), an inhibitor of nitric oxide biosynthesis. 2. In the absence of L-NAME, the low dose of BRL 38227 caused slight hypotension and tachycardia, accompanied by small increases in mesenteric and hindquarters blood flow only. However, there were increases in renal, mesenteric and hindquarters vascular conductances. L-NAME had no effect on any of these responses. 3. The high dose of BRL 38227 caused substantial hypotension and tachycardia. Renal and hindquarters flows did not change significantly, but there was a marked increase in mesenteric flow. There were only modest increases in renal and hindquarters vascular conductances but a substantial mesenteric vasodilatation. In the presence of L-NAME, there was a slight reduction of the latter but no other changes in the responses to BRL 38227. 4. In the absence of L-NAME, the low dose of adrenaline caused slight hypotension but a marked tachycardia. There were no changes in renal or mesenteric blood flow but a clear-cut increase in hindquarters flow. Renal and mesenteric vascular conductances showed only small rises, in contrast to the substantial hindquarters vasodilatation. In the presence of L-NAME, there was significant attenuation of the tachycardia and of the increases in hindquarters flow and vascular conductance in response to adrenaline.5. The high dose of adrenaline caused marked hypotension and tachycardia. Renal flow did not change, but there was a fall in mesenteric and a marked rise in hindquarters flow. Renal vascular conductance showed a slight increase but mesenteric vascular conductance did not change significantly, whereas there was a substantial hindquarters vasodilatation. In the presence of L-NAME, adrenaline caused an increase in blood pressure but no significant change in heart rate; the renal vasodilatation was abolished, there was a mesenteric vasoconstriction, and the hindquarters vasodilatation was markedly reduced. L-NAME also attenuated the tachycardia induced by adrenaline in animals with no cardiac baroreflexes.6. The present results indicate that L-NAME-sensitive mechanisms are involved in the vasodilator and tachycardic effects of adrenaline. The relative lack of effect of L-NAME on responses to BRL 38227 indicates that the changes in the responses to adrenaline were not non-specific or due to changes in haemodynamic status caused by L-NAME. The results raise the possibility that the 'hypertensinogenic' properties of endogenous adrenaline could be amplified when nitric oxide biosynthesis is impaired.

Antagonistic Effect of Human α-Calcitonin Gene–Related Peptide (8–37) on Regional Hemodynamic Actions of Rat Islet Amyloid Polypeptide in Conscious Long-Evans Rats

Rat synthetic amidated islet amyloid polypeptide (IAPP) was infused into conscious Long-Evans rats chronically instrumented for the measurement of regional hemodynamics. Rat IAPP (0.25-2.5 nmol.kg-1.min-1) had dose-dependent tachycardiac and hypotensive effects. Renal blood flow increased at all dose levels in association with incremental rises in renal vascular conductances. Hindquarters blood flow and vascular conductance increased at the higher dose levels, but mesenteric blood flow fell with mean arterial blood pressure (i.e., there was no change in mesenteric vascular conductance). Concurrent infusion of 25 nmol.kg-1.min-1 human alpha-calcitonin gene-related peptide (CGRP) (8-37) abolished the hypotensive, tachycardiac, and renal and hindquarters vasodilator effects of rat IAPP, and during administration of both peptides, there was a transient renal and sustained mesenteric vasoconstriction. When the infusion of human alpha-CGRP (8-37) was stopped, the effects of the continued infusion of rat IAPP were reestablished. The results indicate that the reported ability of IAPP to induce insulin resistance cannot be due to decreased skeletal muscle blood flow. In addition, human alpha-CGRP (8-37) is an effective antagonist of the hemodynamic actions of rat IAPP. Because it has been shown previously that human alpha-CGRP (8-37) antagonizes the hemodynamic effects of human alpha-CGRP, these results, collectively, indicate that human alpha-CGRP and rat IAPP might act on the same receptor at which human alpha-CGRP (8-37) is an effective antagonist or that the latter is a nonselective antagonist of separate receptors on which human alpha-CGRP and rat IAPP act.

The effects of endothelin‐1 and NG‐nitro‐l‐arginine methyl ester on regional haemodynamics in conscious rats with streptozotocin‐induced diabetes mellitus

1. Resting haemodynamic status and responses to endothelin-1 (0.0004, 0.04, 0.4 nmol kg-1) and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1) were assessed in conscious, Wistar rats treated with streptozotocin (STZ) to induce diabetes mellitus, and in control animals treated with saline. 2. In the resting state, STZ-treated rats had a bradycardia relative to control animals (291 +/- 13 and 337 +/- 10 beats min-1, respectively), but mean arterial blood pressures were the same in the two groups (STZ-treated 109 +/- 3; control 114 +/- 4 mmHg). However, the STZ-treated rats had raised renal (105 +/- 9 units) and mesenteric (114 +/- 16 units) vascular conductances and reduced hindquarters vascular conductance (26 +/- 4 units) relative to control rats (renal, 80 +/- 6; mesenteric, 75 +/- 7; hindquarters, 37 +/- 3 units). 3. Increasing doses of endothelin-1 caused similar, early falls and subsequent rises in mean arterial blood pressures in both groups of rats. Although there were initial hindquarters vasodilatations with endothelin-1 that were not different in STZ-treated and control rats, there were subsequent renal and mesenteric vasoconstrictions that were greater in the former. Hence, the similar rises in mean arterial blood pressures must have been accompanied by a greater reduction in cardiac output in the STZ-treated rats. 4. L-NAME caused similar renal and mesenteric vasoconstrictions in control and STZ-treated rats, but there was a smaller pressor effect and an attenuated hindquarters vasoconstrictor response to L-NAME in STZ-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regional haemodynamic effects of the non-peptide angiotensin II antagonist, DuP 753, in water-replete and water-deprived brattleboro rats

Regional haemodynamic effects of DuP 753 were assessed in conscious unrestrained Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturised pulsed Doppler flow probes and intravascular catheters. Responses to DuP 753 were assessed in water-replete animals and in animals following 14h water deprivation to render cardiovascular status dependent on the renin angiotensin system (RAS). In water-replete animals DuP 753 had little effect on mean arterial blood pressure, but there were dose-dependent tachycardias and increases in renal blood flow, associated with vasodilatations. There were also increases in mesenteric blood flow and vascular conductance, but these were not clearly dose-related; DuP 753 had no significant effects on hindquarters haemodynamics. In water-deprived animals DuP 753 caused dose-dependent hypotension, tachycardia, and renal and mesenteric vasodilatations; hindquarters vasodilatation was not dose-dependent. In both conditions, in the presence of DuP 753 (10 mg/kg), captopril had little additional effect. DuP 753 appears to be an extremely effective tool for assessing the role of the RAS in cardiovascular regulation.

Effects of NG‐nitro‐l‐arginine methyl ester or indomethacin on differential regional and cardiac haemodynamic actions of arginine vasopressin and lysine vasopressin in conscious rats

1. Measurements of changes in renal, mesenteric and hindquarters haemodynamics or cardiac haemodynamics in response to i.v. bolus doses of arginine vasopressin (AVP) or lysine vasopressin (LVP, 0.7 and 7.0 pmol) were made in conscious, chronically-instrumented Long Evans rats. 2. In some experiments AVP and LVP were administered during an infusion of NG-nitro-L-arginine methyl ester (L-NAME; 1.0 or 0.3 mg kg-1 h-1) to determine whether or not inhibition of nitric oxide production influenced the cardiovascular effects of the peptides. In other experiments, indomethacin (bolus dose of 5 mg kg-1 followed by infusion at 5 mg kg-1 h-1) was given to determine the possible involvement of cyclo-oxygenase products in the responses to AVP and LVP. 3. Under control conditions, the lower dose of LVP had significantly greater effects than AVP on heart rate, mean arterial blood pressure, renal, mesenteric and hindquarters conductances, total peripheral conductance, cardiac index, peak aortic flow and +dF/dtmax. The higher dose of LVP had significantly greater effects than AVP on all variables (i.e. including stroke index and central venous pressure). 4. In the presence of L-NAME (1 mg kg-1 h-1) there was a sustained increase in mean arterial blood pressure (+23 +/- 3 mmHg) and reductions in mesenteric (-38 +/- 4%) and hindquarters (-30 +/- 6%) vascular conductances. Under these conditions the difference in the pressor effects of AVP and LVP was abolished, but their differential effects on regional and cardiac haemodynamics persisted. This dose of L-NAME did not change cardiac baroreflex sensitivity. 5. During infusion of L-NAME at a lower rate (0.3mgkg-th-1), baseline cardiovascular status was unchanged and regional haemodynamic effects of AVP and LVP were enhanced, but the differences in the regional vasoconstrictor responses to the two peptides persisted. 6. Indomethacin (5 mg kg-1 bolus, then 5 mg kg- 'h-1 infusion) augmented the renal vasoconstrictor responses to AVP and LVP, but abolished the difference in the hindquarters vasoconstrictor responses to the two peptides. However, the differences in the pressor and the renal and mesenteric vasoconstrictor effects of AVP and LVP still occurred in the presence of indomethacin. 7. The results indicate that AVP normally has lesser cardiovascular effects than LVP but this difference does not seem to be due to more effective stimulation of nitric oxide-mediated or cyclo-oxygenase-dependent vasodilator mechanisms by AVP than LVP.

Mechanisms contributing to the differential haemodynamic effects of bombesin and cholecystokinin in conscious, Long Evans rats

1. Long Evans rats were chronically instrumented with intravascular catheters and pulsed Doppler probes to assess changes in renal, mesenteric and hindquarters blood flows and vascular conductances in response to bombesin (2.5 micrograms kg-1, i.v.) and cholecystokinin (CCK) (0.5 and 5.0 micrograms kg-1, i.v.). 2. Bombesin caused an increase in heart rate and blood pressure, together with a transient renal vasoconstriction and prolonged mesenteric vasodilatation; there was an early hindquarters vasodilatation followed by vasoconstriction. 3. In the presence of phentolamine, bombesin caused a fall in blood pressure due to enhanced hindquarters vasodilatation; these effects were reversed by propranolol and hence were possibly due to circulating adrenaline acting on vasodilator beta 2-adrenoceptors. 4. During concurrent administration of phentolamine, propranolol and atropine, bombesin caused prolonged tachycardia and a rise in blood pressure. The renal vasoconstrictor and mesenteric vasodilator effects of bombesin were not reduced under these conditions and thus probably were direct and/or indirect non-adrenergic, non-cholinergic (NANC) effects. 5. CCK caused dose-dependent increases in blood pressure accompanied by renal, mesenteric and hindquarters vasoconstriction followed, after the higher dose, by vasodilatations. The lower dose of CCK increased heart rate but there was a bradycardia followed by a tachycardia after the higher dose. 6. Experiments with antagonists as described above indicated the pressor effect of CCK was mediated largely through alpha-adrenoceptors, as were the mesenteric and hindquarters vasoconstrictor effects; CCK exerted NANC negative chronotropic effects. 7. All the effects of CCK were markedly inhibited by L364,718. This observation, and the finding that L364,718 had no effect on the responses to bombesin, together with the dissimilarities in the regional haemodynamic effects of exogenous CCK and bombesin, indicate that the cardiovascular actions of the latter were not dependent on the release of endogenous CCK.

Regional Haemodynamic Effects of Captopril, Enalaprilat and Lisinopril in Conscious Water-Replete and Water-Deprived Brattleboro Rats

1. The regional haemodynamic effects of intravenous bolus doses of captopril, enalaprilat and lisinopril were assessed in conscious Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturized pulsed Doppler probes and intravascular catheters. 2. Responses to incremental doses of each drug (spanning the median effective dose for the inhibition of the pressor response to angiotensin I) were examined in both water-replete and water-deprived states. 3. In the water-replete state, the haemodynamic profiles of captopril, enalaprilat and lisinopril were generally similar, with incremental doses causing rises in mesenteric and renal flow and, to a lesser extent, hindquarters flow. There were small tachycardias and only slight falls in mean blood pressure. 4. In the water-deprived state, the effects of all three drugs were greatly enhanced; tachycardic and hypotensive effects occurred together with increases in mesenteric, renal and hindquarters flows. However, for renal flow and renal vascular conductance the effectiveness of the drugs decreased in the order enalaprilat greater than captopril greater than lisinopril, whereas for mesenteric flow and mesenteric vascular conductance the order was captopril greater than enalaprilat greater than lisinopril. 5. Since marked haemodynamic actions were seen with doses one-tenth of the median effective dose for the inhibition of the pressor effect of angiotensin I, it is likely these effects were due to inhibition of angiotensin-converting enzyme, although not necessarily to inhibition of angiotensin II production.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional haemodynamic changes during oral ingestion of NG‐monomethyl‐l‐arginine or NG‐nitro‐l‐arginine methyl ester in conscious Brattleboro rats

Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hindquarters vascular conductances fell. These changes showed diurnal rhythms, probably related to the nocturnal habits of rats. In separate groups of animals spontaneous oral ingestion of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) or NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg ml-1) caused marked hypertension but no significant bradycardia. Compared to control animals, rats drinking L-NMMA for 9 h showed significantly greater mesenteric and hindquarters vasoconstrictions, and rats drinking L-NAME showed greater vasoconstrictions in all 3 vascular beds.

Responses to hypotension in conscious rats with chronic portal venous hypertension

Heart rate, mean arterial pressure, and vascular conductance response to intravenous nitroprusside were compared in conscious, unrestrained portal vein-stenosed and sham-operated rats chronically instrumented for pulsed Doppler flowmetry. Ten to twelve days after portal vein stenosis, portal venous pressures were elevated and resting heart rates were greater. Portal vein-stenosed animals' depressor responses to nitroprusside were similar to those of sham-operated animals, despite a 41% reduction in their tachycardic response to arterial hypotension. Skeletal muscle vascular bed reflex responses to nitroprusside-induced hypotension were significantly attenuated in the portal vein-stenosed group, whereas their renal artery and superior mesenteric artery responses resembled that of the sham-operated group. After ganglionic blockade, tachycardic responses to hypotension were abolished, but portal vein-stenosed rats' heart rates remained greater than sham-operated rats. Comparisons of arterial pressure changes, renal artery, abdominal aorta, and superior mesenteric artery vascular conductance changes after ganglionic blockade revealed no differences in neurogenic vascular tone between groups. Ganglionic blockade enhanced nitroprusside depressor responses and increased vascular conductance responses to nitroprusside in both treatment groups while abolishing the between group difference in the skeletal muscle baroreflex response. These findings indicate that chronic prehepatic portal vein stenosis with portal venous hypertension results in reduced reflex tachycardic and skeletal muscle baroreflex responses to nitroprusside-induced hypotension.

Pressor responses in conscious rats with chronic portal venous hypertension.

Heart rate, mean arterial pressure (MAP), and vascular conductance responses to graded phenylephrine (PE) infusions were compared in conscious, unrestrained portal vein-stenosed (PS), and sham-operated (SO) rats chronically instrumented for pulsed Doppler flowmetry. Ten days after stenosis, MAP was lower in PS than in SO, and PS heart rates were higher. Pressor sensitivity to PE was attenuated 70%, and bradycardic responses to increases in MAP were 47% greater in PS. Abdominal aorta vascular bed conductance sensitivity was reduced 84%, and renal artery sensitivity was reduced 29% in PS compared with SO, whereas the superior mesenteric artery conductance response was unaffected by portal vein stenosis. After ganglionic blockade, the heart rate of PS remained greater than that of SO, and comparisons of renal artery, abdominal aorta, and superior mesenteric artery vascular conductances revealed no significant differences in neurogenic vascular tone. Differences between PS and SO pressor responses were abolished by ganglionic blockade, as were differences in vascular bed conductance responses. These findings suggest that a greater bradycardic response and greater baroreflex-mediated withdrawal of sympathetic tone from skeletal muscle and renal vascular beds were responsible for the decreased pressor sensitivity observed in PS animals.

Analysis of factors that contribute to cardiovascular changes induced in the cat by graded levels of systemic hypoxia.

1. In cats anaesthetized with Saffan, which does not block afferent activation of the brain stem defence areas, we have analysed the cardiovascular changes induced by 3 min periods of graded systemic hypoxia (fraction of O2 in inspirate, Fi,O2, 0.15, 0.12, 0.08, 0.06). 2. At light levels of Saffan anaesthesia, hypoxia (particularly Fi, O2 0.08 and 0.06) or selective stimulation of carotid chemoreceptors evoked the pattern of tachycardia, decrease in renal and mesenteric vascular conductance (RVC, MVC), but increase in femoral vascular conductance (FVC) which is characteristic of the alerting-defence response. This supports our view that activation of the defence areas is an integral part of the response to systemic hypoxia. 3. Hypoxia also induced an increase in frequency of augmented breaths which was graded with the level of hypoxia: 0.6 min-1 at Fi, O2 0.21 to 1.1 min-1 at Fi, O2 0.06; in some cats each of these was accompanied by a transient fall in arterial pressure (ABP) and increase in FVC. It is proposed that these responses were all part of a reflex elicited by lung irritant receptors and facilitated by peripheral chemoreceptors. However, their low rate of occurrence and the liability of the vasodilatation suggests they do not make major contributions to the overall response. 4. The above short-lasting responses were superimposed upon gradual changes whose magnitudes were graded with the level of hypoxia: hyperventilation, slight tachycardia, but bradycardia at Fi, O2 0.6, small increases in ABP, FVC and MVC allowing femoral and mesenteric blood flow to increase, but decreases in RVC which maintained renal blood flow constant. 5. Vagotomy had no significant effect on these changes. Further, hyperinflation of the lungs with pressures of 10 mmHg evoked the Breuer-Hering reflex but had no noticeable cardiovascular effect. It is proposed that, in the cat, reflex tachycardia and vasodilatation elicited by lung stretch receptors play no significant part in the response to hypoxia. 6. By contrast, after pneumothorax, with ventilation and thereby arterial PCO2 (Pa, CO2) maintained constant, graded hypoxia produced graded bradycardia, decrease in MVC and RVC and no change in FVC. Taken together, these results suggest that in the spontaneously breathing cat, the response to hypoxia is dominated by the effects of hypocapnia secondary to hyperventilation, which by inhibiting peripheral and central chemoreceptor activity effectively counteracts the primary bradycardia and peripheral vasoconstriction elicited by hypoxic stimulation of peripheral chemoreceptors. 7. These proposals are compared with those drawn for other species.

Direct observations of effects of baroreceptor stimulation on mesenteric circulation of the rat.

1. In anaesthetized rats, supramaximal baroreceptor stimulation by carotid sinus inflation evoked a reflex fall in systemic arterial pressure and an increase in gross mesenteric vascular conductance, but no significant change in gross mesenteric blood flow. 2. Principal arteries (80-350 microns internal diameter (i.d.)) which supply the intestine and mesentery, small arteries (30-40 microns) and some terminal arterioles (18-30 microns) of the mesentery showed a diameter increase beginning with the fall in arterial pressure, but remaining terminal arterioles and precapillary arterioles (10-18 microns) showed a diameter increase beginning when arterial pressure neared its lowest level. 3. Application of phentolamine to the mesentery abolished diameter increases that began with the reflex fall in arterial pressure. Thereafter, 50% of small arteries and terminal and precapillary arterioles showed diameter increases that began when the fall in arterial pressure neared its zenith. 4. It is proposed that the proximal arterial vessels, which are known to be sympathetically innervated, predominantly showed dilatation mediated by reflex inhibition of sympathetic tone, while more distal arterioles showed myogenic dilatation secondary to the fall in systemic arterial pressure. 5. Small veins (30-50 microns) of the mesentery and principal veins (100-560 microns) that drain mesentery and intestine also showed a diameter increase beginning with the reflex fall in systemic arterial pressure. Since they are known to have a sympathetic noradrenergic supply, and in the absence of changes in mesenteric blood flow likely to cause passive changes in venous diameter, they apparently showed dilatation due to inhibition of sympathetic tone. 6. The above responses are all compatible with, and so suggest underlying mechanisms for, changes in blood flow, regional blood volume, and capillary filtration evoked by baroreceptor stimulation in studies of whole mesenteric circulation, i.e. intestine as well as mesentery.

Direct observations of responses of mesenteric microcirculation of the rat to circulating noradrenaline.

The responses of mesenteric microcirculation of the rat to circulating noradrenaline were studied by in vivo microscopy, using a photo-electric device placed on a television monitor to measure changes in diameter of individual vessels. Blood flow was measured in the anterior mesenteric artery with an electromagnetic flow transducer, mesenteric vascular conductance was computed on-line from mesenteric artery flow and arterial pressure. I.V. injection of noradrenaline induced a decrease in diameter of arterioles (less than 30 microns) which began simultaneously with the rise in arterial pressure and averaged 15% at 15-20 s. By contrast small and principal arteries (30-40 microns and 80-350 microns respectively) generally showed a diameter increase which averaged 10% and began at the peak of the pressor response. Venules and veins (12-560 microns) showed a diameter decrease which averaged 12-15% at 25-30 s. Meanwhile mesenteric vascular conductance fell by 65-75% in 10 s and rose to 30-50% above control in 25-30 s. The diameter increases of small and principal arteries were not reflex dilator responses initiated by the rise in systemic arterial pressure, nor due to beta-adrenoreceptor stimulation. However, local application of phentolamine abolished responses of all sections of the vascular tree indicating that they all depended on activation of alpha-adrenoreceptors. During I.V. infusion of noradrenaline small arteries showed a maintained increase in diameter which began at the peak of the pressor response, while arterioles initially decreased in diameter but then relaxed, often attaining resting diameter before infusion ceased. Meanwhile mesenteric flow and conductance decreased transiently, but then returned to near control levels, i.e. 'autoregulatory escape' occurred. It is argued that noradrenaline induced alpha-mediated contraction of all sections of the vascular tree; the tendency of arteries to constrict was counteracted by the rise in intravascular pressure caused by arteriolar constriction, active constriction of venous vessels may have been augmented by passive collapse secondary to arteriolar constriction. The secondary relaxation of arterial vessels reflects an inherent property of their smooth muscle to relax from the constrictor influence of noradrenaline and is more marked in proximal than distal vessels. It is proposed that the initial decrease in mesenteric vascular conductance in response to circulating noradrenaline may be attributed to active constriction of distal arterioles and the secondary increase in conductance ('escape') to secondary relaxation of more proximal arterial vessels.