Mesenteric Vascular Resistance Research Articles

Cromakalim, a Potassium Channel Activator

Studies have been performed to compare the cardiovascular haemodynamic profiles of the potassium channel activator, cromakalim (BRL 34915), with those of pinacidil and nicorandil. In conscious renal hypertensive cats, cromakalim was 10 times more potent than pinacidil as an antihypertensive agent while nicorandil was 10 times less potent than pinacidil. Cromakalim and pinacidil had a similar duration of action while nicorandil was short acting. In anaesthetised cats, hypotension evoked by intravenous infusions of cromakalim, pinacidil, or nicorandil was associated with a decrease in mesenteric vascular resistance but only cromakalim produced a marked reduction in renal vascular resistance. Cromakalim, pinacidil, and nicorandil were highly specific as inhibitors of tension in vascular (rabbit portal vein) (IC50 = 2.1 x 10(-8), 4.6 x 10(-8), and 1.3 x 10(-6)M, respectively,) rather than cardiac (rabbit papillary muscle), tissue. In view of its antihypertensive efficacy, specificity for vascular tissue, and beneficial effect upon renal haemodynamics, the potassium channel activator, cromakalim, has advantages in its profile of activity compared to pinacidil and nicorandil.

Studies on the Mechanisms of the Development of Tolerance to the Hypotensive Effects of Fenoldopam in Rats

In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, intravenous (i.v.) infusions of fenoldopam (2.5 - 160.0 micrograms/kg/min during 15 min) decreased mean carotid artery blood pressure, total peripheral, hindquarter, renal, and mesenteric vascular resistances and increased renal blood flow strongly. The hypotensive effects attained a maximum within the first 3 min of infusion but waned by greater than 30% at the end of fenoldopam administration. This tolerance was observed for calculated total peripheral and hindquarter vascular resistances and to a lesser extent for mesenteric resistance. However, it was absent on the renal vascular bed. Pretreatment with either enalapril, pepstatine, or bilateral nephrectomy significantly increased the hypotensive response to fenoldopam and attenuated the development of tolerance. In conscious spontaneously hypertensive rats (SHR), enalapril potentiated strongly the small blood pressure-lowering activity of fenoldopam. The fall in blood pressure produced by fenoldopam was specifically blocked by SCH 23390, an antagonist of DA-1 dopamine receptors. In normotensive vasopressin-supported pithed rats given phenoxybenzamine plus propranolol, fenoldopam, like SCH 23390, blocked the vasodepressor effects of i.v. bolus injection of dopamine and fenoldopam. In pithed rats, fenoldopam evoked a pressor response that was significantly reduced by enalapril, SCH 23390, or bilateral nephrectomy. In conclusion, fenoldopam exerts DA-1 agonist and antagonist effects. The latter property, together with the activation of the renin-angiotensin system, appears to be responsible for the development of tolerance to the fenoldopam evoked-hypotension. The lack of a tolerance at the level of the renal vascular bed is possibly due to the existence of a large population of DA-1 receptors in this region.

Cardiovascular effects of central calcitonin gene-related peptide in conscious rats.

Calcitonin gene-related peptide (CGRP) is a potent peripheral vasodilator. In the present study, the cardiovascular effects of centrally administered CGRP were examined in conscious, normotensive rats. The rats were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow in the conscious animals. Injection of increasing doses of CGRP (0.3 to 3.0 micrograms/kg) in the lateral cerebroventricles transiently increased arterial pressure (maximal change = 13 +/- 3 mm Hg) and markedly increased heart rate (maximal increase = 88 +/- 10 b/min). The heart rate response was sustained over a period of 20 to 30 minutes. Central CGRP decreased hindquarter vascular resistance but had no effect on renal or mesenteric vascular resistances. In contrast, intravenous injections of CGRP reduced arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The tachycardia response to central CGRP was attenuated by pretreatment with propranolol or hexamethonium, indicating that the heart rate response was mediated, in part, through increases in cardiac sympathetic tone. These data indicate that central CGRP may alter cardiovascular function through alterations in sympathetic outflow.

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

The mechanisms mediating the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricular (i.c.v.) injection of TRH (8 pmol-80 nmol/kg) induced dose-dependent increases in mean arterial pressure, heart rate, and cardiac index. Hindquarter blood flow increased due to vasodilation, while an increase in renal and mesenteric vascular resistance caused a decrease in blood flow in the respective organs. The plasma levels of norepinephrine and epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. The cardiovascular actions of i.c.v. TRH were not influenced by blockade of the renin-angiotensin system or vasopressin receptors. The ganglion blocker chlorisondamine and the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c.v. TRH. Propranolol (2 mg/kg i.v.) blocked the TRH-induced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodilation induced by TRH was also blocked by the selective beta 2-adrenoceptor antagonist ICI 188,551 (1 or 2 mg/kg i.v.), while the beta 1-adrenoceptor blocker practolol (10 mg/kg i.v.) had no effect on the hindquarter vasodilation produced by TRH but totally blocked the increase in cardiac index. In adrenal demedullated rats, the systemic hemodynamic effects of i.c.v. TRH were diminished along with the decrease in renal blood flow and increase in renal vascular resistance; however, the increase in hindquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetic blocker bretylium. The renal vasoconstriction induced by i.c.v. TRH was not abolished by renal denervation. In sinoaortic debuffered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data suggest that the putative neurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both the sympathetic nerves and the adrenal medulla. A pivotal role for beta 2-adrenoceptors in mediation of hindquarter vasodilation is also demonstrated.

Evidence for two functionally distinct vasomotor subregions of rostral ventral medulla.

We examined two functionally and anatomically distinct subregions of rostral ventral medulla, rostral ventrolateral medulla (RVLM, 2 mm lateral to midline) and an area we term rostral ventromedial medulla (RVMM, 1mm lateral to midline). Reducing tidal volume attenuated the depressor response to microinjection of lidocaine (200nl, 4%) into RVLM, but not into RVMM. Lidocaine reduced renal (RVR), mesenteric (MVR), and hindquarter (HQVR) vascular resistances, when injected into both sites, however HQVR was markedly reduced when RVMM was blocked. Selective stimulation with microelectrodes increased RVR, MVR, and HQVR, with RVMM producing the strongest response in HQVR and RVLM the strongest effect on RVR. Cardiovascular responses to stimulation of RVLM required the integrity of RVMM, however, the converse was not found. The integrity of RVMM, but not RVLM, was required for the cardiovascular responses produced by electrical stimulation of lateral hypothalamus. Together, these data suggest that RVLM and RVMM are both important for tonic regulation of vasomotor tone, however, these sites differ in their responses to afferent input and in the control of regional vascular resistances.

Effect of a Prostacyclin Derivative (Iloprost) on Regional Blood Flow, Sympathetic Nerve Activity, and Baroreceptor Reflex in the Conscious Rat

We have investigated the hemodynamic actions of iloprost, a stable prostacyclin derivative, in conscious, chronically instrumented rats. Given intravenously by 10-min infusions at doses ranging from 0.0375 to 4 micrograms/min, iloprost lowered mean arterial blood pressure in a dose-dependent and reversible fashion. The effects on blood pressure were accompanied by increases in heart rate (HR); splanchnic nerve activity (SpNA, direct recording); and mesenteric, renal, and hindlimb blood flow (Doppler probes). Doses below the depressor threshold already reduced mesenteric and hindlimb vascular resistance without affecting HR. The reduction of hindlimb resistance outlasted the iloprost infusion period. Chronic sinoaortic deafferentation (SAD) almost abolished the tachycardic reflex responses to intravenous sodium nitroprusside. The reflex increases in SpNA to intravenous iloprost were also largely prevented in SAD animals, but the tachycardic effects of iloprost persisted. In addition, neither beta 1-adrenoceptor blockade alone nor complete cardiac autonomic blockade prevented the heart rate responses to iloprost. Our results show that iloprost is a potent vasodilator that preferentially reduces hindlimb vascular resistance. Low doses of the drug increase regional blood flow without affecting blood pressure or heart rate. The tachycardic effects at higher doses cannot be explained by baroreceptor reflex (BRR) activation alone; they instead suggest a direct action on the heart. The dissociation between vasodilator and depressor effects at low doses may contribute to the therapeutic benefit of the drug in the treatment of vascular disease.

Vasoconstrictor and vasodilator sites within anteroventral third ventricle region.

Previous studies have shown that electrical stimulation of the rat anteroventral third ventricle (AV3V) region produces a characteristic pattern of hemodynamic effects, i.e., renal and mesenteric vasoconstriction, and hindquarters vasodilation. In the present study, we localized the vasoconstrictor and vasodilator effects to specific subregions of the AV3V. In urethan-anesthetized rats prepared with arterial catheters and pulsed Doppler flow probes, we assessed the effects of electrical stimulation of four nuclei within AV3V on mean arterial pressure and renal, mesenteric, and hindquarters resistance. These nuclei were the organum vasculosum lamina terminalis (OVLT), ventral nucleus medianus (median preoptic nucleus), anterior (precommissural) nucleus medianus (median preoptic nucleus), and periventricular preoptic nuclei. Stimulation was carried out by use of a tungsten microelectrode. Stimulation of the OVLT consistently provoked stimulus-locked increases in arterial pressure coupled with increases in mesenteric and renal vascular resistance. Ganglionic blockade with chlorisondamine prevented these responses, demonstrating that they were mediated neurogenically. Stimulation of the three remaining nuclei produced decreases in arterial pressure, hindquarters vasodilation, and little change in mesenteric and renal vascular resistance. No changes in heart rate were observed with stimulation of any of the four nuclei. These results suggest that the vasoconstrictor and pressor functions of the AV3V region are localized in or near the OVLT region, whereas the remaining nuclei of the AV3V region mediate vasodilator and depressor responses.

Effects of atrial natriuretic factor on the vasoconstrictor actions of the renin-angiotensin system in conscious rats.

Previous studies have indicated that the hypotensive effects of atrial natriuretic factor were enhanced in renin-dependent hypertensive rats, suggesting that the atrial peptides may antagonize the vasoconstrictor effects of the renin-angiotensin system. The present study was designed to define further the interaction between atrial natriuretic factor and the renin-angiotensin system by examining the hemodynamic effects of Wy-47,663, a synthetic human atrial natriuretic factor, in conscious normotensive rats, in renin-dependent (aortic-ligated) hypertensive rats, and in rats made hypertensive by chronic infusion of angiotensin II. Changes in renal and mesenteric blood flow were continuously monitored in the rats using pulsed Doppler flow probes chronically implanted in the animals one week prior to testing. Infusion of increasing doses of Wy-47,663 caused dose-dependent reductions in mean arterial pressure in all three groups of rats, but the depressor responses were significantly greater in renal hypertensive and angiotensin II-infused rats. Renal blood flow tended to increase during the infusion of the atrial peptide in the angiotensin II-treated rats, and renal vascular resistance fell significantly (-37 +/- 6%). However, Wy-47,663 significantly reduced renal blood flow in the normotensive and renal hypertensive rats, while renal vascular resistance was increased (29 +/- 6%) and unchanged (3 +/- 9%), respectively. Mesenteric blood flow was reduced significantly, and mesenteric vascular resistance was increased markedly in all three groups of rats during infusion of the atrial peptide. In a separate group of renal hypertensive rats, the hemodynamic effects of complete blockade of the renin-angiotensin system were assessed by injection of an angiotensin II converting enzyme inhibitor (Wy-44,655).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat.

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.

Sympathetic function in spontaneously hypertensive rats after chronic administration of captopril.

The cardiovascular effects of electrical stimulation of the posterior hypothalamus, intravenous administration of norepinephrine (NE), and direct sympathetic nerve stimulation (SNS) were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) given captopril (osmotic minipump, 1.25 micrograms/h icv) or vehicle for 4 wk beginning at age 7 wk. Mean arterial pressure (MAP) and renal and mesenteric flows (pulsed Doppler flow probes) were monitored in anesthetized rats. Following chronic administration of captopril the MAP was 141 +/- 4 mmHg in SHR receiving captopril and 183 +/- 6 mmHg in SHR receiving vehicle. Posterior hypothalamic stimulation, intravenous NE, and SNS resulted in lesser increases in MAP and renal and mesenteric vascular resistances in SHR treated with captopril. Response curves were shifted to the right, and the initial slopes and rate of change of slopes of the curves were less in captopril-treated SHR than vehicle-treated rats. The decrease in sensitivity to posterior hypothalamic stimulation was greater than the decrease in response to NE or SNS. The decrease in vascular reactivity in captopril-treated SHR was not due to increased sensitivity of the baroreflex for control of vascular resistance nor to a decrease in arterial pressure per se. WKY treated with captopril also showed lesser increases in MAP and renal and mesenteric vascular resistances in response to posterior hypothalamic stimulation, intravenous NE, and SNS. The depressor effects of intracerebroventricular captopril in SHR may be due, in part, to an attenuation in sympathetic vasoconstrictor tone. This attenuation involves both a decrease in vascular smooth muscle responsiveness to NE as well as a decrease in central stimulation of sympathetic outflow.

Differential regulation of regional vascular resistance by the rostral and caudal ventrolateral medulla in the rat

Regional vascular resistance changes were determined following chemical excitation and inhibition of the rostral vasopressor (RVLM) and caudal vasodepressor (CVLM) areas in the ventrolateral medulla. Mesenteric, renal and hindquarter vascular resistances were assessed in paralyzed and artificially ventilated urethane-anesthetized rats instrumented with pulsed Doppler flow probes. Microinjection of the excitatory amino acid λ-glutamate in the RVLM elicited a significant dose-related transient increase in blood pressure, heart rate and resistance of mesenteric, renal and hindquarter vascular beds. A similar dose-related hemodynamic profile was obtained following microinjection of muscimol, a GABAmimetic, in the CVLM. In contrast, significant dose-related decrease in blood pressure, heart rate and resistance in mesenteric and hindquarter vascular beds was observed following glutamate-induced excitation of the CVLM and muscimol-induced inhibition of the RVLM. Changes in renal vascular resistance were inconsistent in this second hemodynamic profile. Intravenous administration of the α 1 adrenergic antagonist, prazosin, abolished all of the hemodynamic effects elicited by excitation of the RVLM except the tachycardia. Intravenous atropine methylnitrate blocked the bradycardia associated with excitation of the CVLM but did not alter the vascular resistance changes. These results indicate that the changes in heart rate did not contribute significantly to the resistance profiles described. The changes in vascular resistance elicited by excitation and inhibition of the RVLM were correlated with increase and decrease in the greater splanchnic nerve activity, respectively. In conclusion, neuron pools in the RVLM and CVLM exert differential effects upon resistance in different vascular beds via changes in sympathetic outflow. The relative balance between the opposing cardiovascular control exerted by the RVLM and CVLM is instrumental in determining basal vascular resistance and the distribution of cardiac output.

Chronic digitalis administration alters mesenteric vascular reactivity.

To characterize any digitalis-induced differences in intestinal blood flow autoregulation, we studied the circulatory responses of the rat intestine in control (n = 7) and chronically digitalized (n = 7) animals. Data were generated from denervated isoperfused small intestinal preparations. Arterial pressure, venous pressure, and oxygen consumption were continuously monitored. Determinations of intestinal blood flow allowed calculation of mesenteric vascular resistance and oxygen consumption. Animals underwent stepwise reductions in arterial pressure and acute venous hypertension (10 to 15 mm Hg). There were no differences in baseline hemodynamic or metabolic parameters in control (C) or digitalized (D) animals. Blood flow and oxygen consumption were autoregulated in both C and D rats until perfusion pressure decreased below 50 mm Hg. The response to acute venous hypertension was different. In D rats, venous hypertension resulted in increased vascular resistance (millimeters of mercury per milliliter per minute per 100 gm) [0.89 +/- 0.05 to 0.97 +/- 0.07; p less than 0.05], whereas C rats demonstrated no change [0.92 +/- 0.08 to 0.95 +/- 0.09]. The decrease in oxygen consumption in D rats (-14%) was slightly but significantly greater than that observed in C rats (-9%). Digitalized rats demonstrated a heightened myogenic response to acute venous hypertension with deleterious effects on vascular resistance and oxygen consumption. This reaction was intrinsic to the mesenteric circulation and not mediated by sympathetic nerves or central reflexes. Nonocclusive mesenteric ischemia in digitalized patients may reflect a similar abnormal response to the acute increases in portal pressure accompanying cardiac failure.

Chronic digitalis administration alters mesenteric vascular reactivity

To characterize any digitalis-induced differences in intestinal blood flow autoregulation, we studied the circulatory responses of the rat intestine in control (n = 7) and chronically digitalized (n = 7) animals. Data were generated from denervated isoperfused small intestinal preparations. Arterial pressure, venous pressure, and oxygen consumption were continuously monitored. Determinations of intestinal blood flow allowed calculation of mesenteric vascular resistance and oxygen consumption. Animals under-went stepwise reductions in arterial pressure and acute venous hypertension (10 to 15 mm Hg). There were no differences in baseline hemodynamic or metabolic parameters in control (C) or digitalized (D) animals. Blood flow and oxygen consumption were autoregulated in both C and D rats until perfusion pressure decreased below 50 mm Hg. The response to acute venous hypertension was different. In D rats, venous hypertension resulted in increased vascular resistance (millimeters of mercury per milliliter per minute per 100 gm) [0.89 ± 0.05 to 0.97 ± 0.07; p < 0.05], whereas C rats demonstrated no change [0.92 ± 0.08 to 0.95 ± 0.09]. The decrease in oxygen consumption in D rats (−14%) was slightly but significantly greater than that observed in C rats (−9%). Digitalized rats demonstrated a heightened myogenic response to acute venous hypertension with deleterious effects on vascular resistance and oxygen consumption. This reaction was intrinsic to the mesenteric circulation and not mediated by sympathetic nerves or central reflexes. Nonocclusive mesenteric ischemia in digitalized patients may reflect a similar abnormal response to the acute increases in portal pressure accompanying cardiac failure.

Effect of T-2 toxin on regional blood flow and vascular resistance in the conscious rat

The acute effect of T-2 toxemia on local blood flow and vascular resistance in hindquarter, mesenteric, and renal vascular beds was continuously measured by the directional pulsed Doppler technique in conscious, male Sprague-Dawley rats. Intravenous injection of T-2 toxin (1 mg/kg) in the conscious rat reduced blood flow and increased vascular resistance in all blood vessels studied but had no significant effect on mean arterial pressure or heart rate. The blood flow in hindquarters gradually decreased to a minimum of −77 ± 9% (mean ±SE) 6 hr after the toxin injection. The hindquarter vascular resistance concomitantly increased to a maximum value of +323 ± 69% above the resistance before toxin administration. Mesenteric and renal blood flow initially increased (slightly) and then gradually decreased. The maximum drop of blood flow, −90 ± 13% and −76 ± 13% for the mesenteric and renal vascular beds, respectively, was achieved 4 hr after T-2 toxin injection and the blood flow values remained low for up to 6 hr. Simultaneously with the impairment of blood flow the mesenteric and renal vascular resistance increased to reach the maximal values of +404 ± 99% and +556 ± 15%, respectively. In addition, plasma renin activity was markedly elevated (+653 ± 160%) at the time of reduced renal blood flow. Intravenous injection of the same value of vehicle (10% ethanol in saline) had no significant effect on any of the cardiovascular variables studied. Two of five rats in the T-2 toxin-treated group died within 5 hr after the T-2 toxin injection and only one animal survived 24 hr while all the control animals survived over 24 hr. The results suggest that strong vasoconstriction in skeletal muscle, mesenteric, and renal vascular beds leads to impairment of local blood flow. The ischemia in vital organs together with the earlier reported decrease in cardiac output by T-2 toxin might then be the cause of rapid death in acute T-2 toxemia.

Hemodynamic, Neural, and Humoral Mechanisms of Aortic Coarctation Hypertension in the Rat

The present study was designed: (a) to examine the contribution of the renin-angiotensin system (RAS) to elevated regional vascular resistance during the onset of aortic coarctation hypertension, and (b) to determine the role of angiotensin II (Ang II)-neural interactions during the maintenance of high arterial pressure (AP). In the first study, rats were instrumented chronically with miniaturized pulsed Doppler flow probes on the right renal and superior mesenteric arteries 3 days prior to complete aortic ligation. After ligation, AP and renal and mesenteric vascular resistances increased significantly. In sham-ligated rats, small increases in AP and decreases in regional vascular resistances were observed. Captopril, administered 6 h postligation, reduced AP and regional vascular resistance in ligated rats to preligation levels, indicating that the RAS was responsible for these acute increases. In the second study, Ang II-neural interactions were examined by treating 12- to 14-day postligation hypertensive rats with captopril or with hexamethonium, a ganglionic blocker, followed by captopril. Depressor responses to captopril were also examined in aortic-ligated rats pretreated with hydralazine. Captopril alone and captopril after hydralazine caused similar reductions in AP (-26 +/- 2% and -27 +/- 1%, respectively). After ganglionic blockade, the depressor responses to captopril were attenuated (-13 +/- 2%). The marked differences in the efficacy of captopril to lower AP in the ganglionic-blocked group of rats suggested that the pressor actions of Ang II were mediated, in part, through indirect actions on the sympathetic nervous system.

Renal Vascular Effects of Dilazep Antagonized by 3-Isobutyl-1-Methyl-Xanthine

The effects of different doses of dilazep on renal hemodynamics, urine formation, and renin release were studied in anesthetized dogs. Intrarenal arterial infusion of dilazep (1 microgram/kg/min) increased renal blood flow, with no change in systemic arterial blood pressure and renal venous plasma renin activity. Renal vasodilation induced by dilazep was completely inhibited by intrarenal arterial infusion of 3-isobutyl-1-methyl-xanthine (IBMX; 11.1 micrograms/kg/min), a potent adenosine receptor antagonist, but not by indomethacin (13 mg/kg i.v.). These results suggest that dilazep has a vasodilatory action in the kidney--one that is independent of the renal renin-angiotensin system. The inhibitory action of IBMX on the dilazep-induced renal vasodilation indicates that the renal vascular effects of dilazep may be exerted by augmentation of endogenous adenosine and mediated through adenosine receptors.

EFFECTS OF CERTAIN I.V. ANAESTHETICS ON LIVER BLOOD FLOW AND HEPATIC OXYGEN CONSUMPTION IN THE GREYHOUND

The effects of increasing concentrations of thiopentone, Althesin and etomidate on liver blood flow and hepatic oxygen consumption were investigated in the anaesthetized greyhound. All three agents studied produced dose-related decreases in general cardiovascular indices such as mean arterial pressure, cardiac output and systemic vascular resistance; all three anaesthetics produced decreases in liver blood flow. During the low rates of infusion with Althesin and etomidate, significant decreases in hepatic arterial blood flow were recorded at a time when the systemic circulation was not significantly affected. Indeed, during the low rates of infusion with each of the three agents, hepatic arterial resistance and mesenteric vascular resistance increased by up to 40% above baseline values. During the high rates of infusion, hepatic arterial and mesenteric vascular resistances either returned to or decreased below control values and the decreases in liver blood flow were a consequence of generalized cardiovascular depression. Despite relatively unchanged hepatic oxygen consumption, all the anaesthetics produced significant decreases in the hepatic oxygen supply.

Role of the autonomic nervous system in the control of heart rate and blood pressure in the defence reaction in conscious dogs

The present study was performed on conscious, chronically instrumented dogs, which underwent selective blockade of sympathetic adrenergic and vagal outflows. Excitements were performed on these animals in normal states (N), after chronic treatment with guanethidine, for sympathetic blockade (SB), after cold vagal blockade (VB), and after combined sympathetic and vagal blockade (SB + VB). Heart rate and arterial blood pressure were monitored in all the experiments, while a group of dogs was also tested with an electromagnetic flowmeter on the superior mesenteric artery. The role of the sympathetic and parasympathetic controls in the defence reaction was assumed from comparison of experiments performed in the presence or in the absence of each (or both) autonomic component(s). In the SB + VB condition, excitement was followed by sudden hypotension, without changes in heart rate. In VB experiments, a brief and transient hypotension appeared, followed by gradually developed hypertension, while heart rate progressively rose in about 5 s; there was no sudden increase in mesenteric vascular resistance, which contrasted with the very marked reaction in N experiments. Under vagal control alone (SB), the stimulus elicited prompt tachycardia and hypertension, followed by a period of moderately reduced blood pressure. We conclude that, while the defence reaction leads to a sudden fall of arterial blood pressure, in the absence of compensatory mechanisms, both branches of the autonomic nervous system play a protective role against hypotension. In addition, the modulation of the vagal outflow, leading to sudden changes in the heart performance, seems to be responsible for the initiation of the overall haemodynamic adjustments following excitements. The possibility that withdrawal of the parasympathetic outflow to the heart may raise arterial blood pressure was verified in a special experiment in which artificial vagal stimulation in a conscious (vagal blocked) dog, was turned off for brief periods, before and after guanethidine. This led to changes in blood pressure and heart rate very similar to those seen at the onset of the defence reaction, both in N and SB conditions.

Nonhomogeneous redistribution of mesenteric blood flow after tolazoline during group B streptococcal sepsis in piglets.

The effect of tolazoline (Tz) on mesenteric blood flow was evaluated in a piglet model of group B streptococcal (GBS) sepsis. GBS infusion decreased cardiac output and mesenteric blood flow equivalently, while increasing systemic and mesenteric vascular resistance. At three doses between 2 and 25 mg/kg, Tz increased cardiac output and decreased systemic vascular resistance. However, at no dose did Tz improve the diminished mesenteric artery blood flow which accompanied GBS sepsis. The potential use of Tz in neonatal sepsis may be limited by its nonhomogeneous redistribution of blood flow.

Analysis of adrenergic responses in the mesenteric vascular bed of the cat; evidence that vascular beta 2-adrenoceptors are innervated.

Responses to sympathetic nerve stimulation and pressor hormones were investigated in the feline mesenteric vascular bed under conditions of controlled blood flow. Sympathetic nerve stimulation and norepinephrine produced frequency- and dose-dependent increases in mesenteric vascular resistance. However, when alpha-receptors were blocked with the non-equilibrium alpha-receptor antagonist, phenoxybenzamine, nerve stimulation and norepinephrine produced frequency- and dose-dependent decreases in mesenteric vascular resistance. These reductions in mesenteric vascular resistance were unchanged after indomethacin or atropine, whereas propranolol converted the mesenteric vasodilator responses to small vasoconstrictor responses. In these studies, responses to a variety of vasoconstrictor agents were enhanced after administration of propranolol. Sotalol, a nonselective beta blocker with little membrane stabilizing activity, also enhanced vasoconstrictor responses. The present data suggest that both alpha- and beta-adrenergic receptors are innervated in the feline mesenteric vascular bed, and that vasodilator responses to norepinephrine and sympathetic nerve stimulation are independent of activation of muscarinic receptors or formation of products in the cyclooxygenase pathway. These data also demonstrate that there is a nonspecific potentiation of intestinal vasoconstrictor responses after beta-adrenergic receptor blockade that is independent of a membrane-stabilizing or receptor-mediated mechanism.