Mesenteric Resistance Research Articles

Isoflurane, and Not Halothane, Increases Mesenteric Blood Flow Supplying Esophageal Ileocoloplasty

Regional ischemia may induce anastomotic leakage or stenosis after esophageal reconstruction using retrosternal interposition of an ileocolic graft. These complications may be related to systemic or local hemodynamic alterations. This study was designed to evaluate the influence of inhalational anesthetic agents on the intestinal circulation supplying these ileocolic grafts. Seven patients (age 30 +/- 5 yr, mean +/- standard deviation [SD]) were studied in the immediate postlaparotomy period. Miniaturized Doppler implantable microprobes were sutured to the single artery supplying the graft and connected to an 8-MHz pulsed Doppler flowmeter. Continuous fentanyl infusion (300 micrograms.h-1) was maintained throughout the study. Measurements were performed at the end of four 30-min periods, which were, successively: first control; isoflurane or halothane anesthesia; second control; and isoflurane or halothane anesthesia. Isoflurane and halothane were administered in cross sequence with end-tidal concentration of 0.8% and 0.5%, respectively, to induce equipotent anesthesia. Both anesthetics induced similar decreases in mean systemic arterial pressure (MAP), cardiac output (CO), and systemic vascular resistance. During isoflurane, mean mesenteric blood flow (MBFm) supplying the graft was increased (+38%; P less than 0.05), and the mesenteric vascular resistance index (MVRI; -44%; P less than 0.05) was decreased, leading to an increase in the MBFm/CO ratio (P less than 0.05). Halothane changed neither the MBFm nor the MBFm/CO ratio, despite a mild decrease in MVRI (-14%; P less than 0.05). Diastolic blood flow velocity increased significantly (2.3 +/- 0.9 vs. 0.8 +/- 0.3 cm.s-1, P less than 0.05) only with isoflurane, suggesting a local vasodilation not observed with halothane.(ABSTRACT TRUNCATED AT 250 WORDS)

Tonic Control of Arterial Pressure and Regional Hemodynamics by Supra-Medullary Sites

We examined the role of pontine sites in the tonic control of vasomotor tone under normal and reduced tidal volumes. Lidocaine was microinjected in pons at the level of the Kölliker-Fuse nucleus (KFN). Injections were made bilaterally 6, 7, 8, and 9 mm below dura, and 0.9 and 2.5 mm lateral to midline. Lidocaine in KFN produced a fall (-14 mmHg) in mean arterial pressure (MAP) at normal and reduced tidal volumes. These effects were mediated primarily by a reduction in hindquarter vascular resistance. Lidocaine into a ventromedial site (8.0 mm beneath dura, 0.9 mm lateral to midline) increased MAP by increasing renal, mesenteric, and hindquarter vascular resistance. After sino-aortic deafferentation (SAD), reduced tidal volume augmented the pressor and blunted the tachycardic responses to lidocaine injected into the ventromedial pons (9.0 mm beneath dura, 0.9 mm lateral to midline). SAD also enhanced the pressor response to lidocaine injected into ventromedial pons. This work demonstrates a role for supra-medullary sites in the tonic control of vasomotor tone.

Beta-2 Adrenoceptor Mediated Vasodilation: Role in Cardiovascular Responses to Acute Stressors in Spontaneously Hypertensive Rats

The present paper summarizes our studies on the role of beta-2 adrenoceptor mediated vasodilatory mechanisms in the cardiovascular defense response of spontaneously hypertensive rats (SHR) and presents new data on the contribution of altered vascular responsiveness to vasodilators. SHR had similar blood pressure but exaggerated plasma norepinephrine (NE) and epinephrine (EPI) responses compared to their normotensive control strain, the Wistar-Kyoto (WKY), while the plasma catecholamine response of the first generation (F1) cross was intermediate. An examination of regional blood flow changes to footshock stress indicated that SHR compared to WKY had greater increases in mesenteric vascular resistance that appeared to be offset by more pronounced decreases in hindquarter vascular resistance. Blockade of beta-2 adrenoceptors, which are densely located in the skeletal muscle vasculature, led to greatly increased pressor responses to stress in SHR but was without effect in WKY. Results of our current work indicate that this response is due to increased stimulation of the beta-2 adrenoceptors during stress rather than to increased vascular reactivity. These results indicate that in SHR relative to WKY, the exaggerated sympatho-adrenal response to stress does not produce greater blood pressure responses because of the offsetting influences upon vasodilation and vasoconstriction.

Anatomical Localization of the Binding and Functional Characterization of Responses to Dopexamine Hydrochloride in the Rat Mesenteric Vasculature

Dopamine receptors of the DA1 subtype have been identified in mesenteric blood vessels, stimulation of which leads to vasodilation. In this study, we have determined the anatomical localization of dopexamine-hydrochloride-binding sites and carried out functional characterization of responses to this DA1-receptor and beta 2-adrenoceptor agonist in rat mesenteric vasculature. Autoradiographic studies showed the presence of [3H]-dopexamine-binding sites in all the different layers of the mesenteric artery. The DA1 receptor antagonist, SCH 23390 (IC50 = 4.9 mumol/l), and the beta-adrenoceptor antagonist, propranolol (IC50 = 6.0 mumol/l), inhibited the binding of dopexamine. The inhibitory effect of these compounds on dopexamine binding was selective for different regions of the mesenteric artery. Also, dopexamine produced concentration-related increases in cAMP formation in membrane particles from superior mesenteric artery and its main branches. The presence of both SCH 23390 and propranolol was required to completely abolish dopexamine-induced increases in cAMP formation. In functional studies, dopexamine (1 and 3 micrograms/kg/min) produced dose-related increases in mesenteric blood flow (23 and 38%, respectively) which were accompanied by concomitant decreases in the calculated mesenteric vascular resistance. As seen with increases in cAMP, the vascular responses to dopexamine could be completely abolished only by prior treatment with both SCH 23390 and propranolol. These results suggest that in mesenteric vasculature of rat dopexamine binds primarily to DA1 receptors and beta 2-adrenoceptors. The activation of these receptors by dopexamine leads to vasodilation which is mediated by an increase in the intracellular levels of cAMP.

Atrial natriuretic peptide infusion causes vasoconstriction after autonomic blockade in conscious dogs

Many studies have shown that atrial natriuretic peptide (ANP) reduces mean arterial pressure (MAP) in conscious animals by lowering cardiac output (CO) with no change or even increased total peripheral resistance (TPR). Because ANP is thought to be a vasodilator, the lack of fall in TPR in conscious animals is generally considered to be due to autonomic reflex increases in vascular resistance. In the present study in conscious, trained, chronically instrumented dogs (n = 7), we measured hemodynamic and renal excretory responses to 30-min infusions of alpha-human ANP (alpha hANP; 25, 50, and 100 ng.kg-1.min-1) in the presence and absence of autonomic nervous system blockade using the ganglion blocking agent pentolinium. In the absence of blockade, MAP and CO fell, whereas TPR rose with alpha hANP infusions, but these changes did not reach significance. There were significant increases in renal vascular resistance (RVR; 16-25%) and mesenteric vascular resistance (MVR; 14-40%). During autonomic nervous system blockade, alpha hANP caused dose-related reductions in MAP (7-12%), due to falls in CO (13-34%). Remarkably, the absence of autonomic reflex responses exposed substantial dose-related increases in TPR (5-33%). Autonomic blockade did not alter the ANP-induced increases in MVR but did abolish the rises in RVR. In summary, ANP caused vasoconstriction in mesenteric vasculature and substantial vasoconstriction in other nonrenal areas, independent of autonomic reflexes.

Cardiovascular effects of posterior hypothalamic stimulation in baroreflex-denervated rats

The overall purpose of this study was to examine the effect of sinoaortic baroreceptor denervation (SAD) on the cardiovascular and sympathetic outflow responses to electrical stimulation of the posterior hypothalamus. In anesthetized rats that had undergone SAD 7-10 days before experimentation, electrical stimulation of the posterior hypothalamus elicited greater increases in mean arterial pressure, iliac vascular resistance, mesenteric vascular resistance, and lumbar sympathetic nerve activity than in sham-operated baroreceptor-intact animals. Similarly, the pressor effects of intravenous norepinephrine were also augmented in the baroreceptor-denervated group compared with the baroreceptor-intact group. When posterior hypothalamic and intravenous norepinephrine pressor stimuli, which produced equivalent pressor responses in sham-operated baroreceptor-intact animals, were compared in baroreceptor-denervated animals, the pressor effects of the central hypothalamic stimulus were enhanced to a greater degree than the norepinephrine pressor effects. These data provide evidence that arterial baroreceptor reflexes exert greater buffering of pressor stimuli initiated from the central nervous system compared with pressor responses due to peripheral vascular vasoconstrictor agents.

Cardiovascular responses to exercise in the rat: role of corticotropin-releasing factor

The effects of intracerebroventricular (icv) administration of a corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical CRF, on systemic and regional hemodynamic adjustments to exercise were studied in conscious rats. On consecutive days, rats received saline icv, alpha-helical CRF icv, and no treatment 30 min before treadmill exercise (TMX). Increases in heart rate (HR) and mean arterial pressure (MAP) in response to TMX (16.1-28.6 m/min) were similar after icv administration of saline or no treatment. In rats receiving saline icv or no treatment, estimated vascular resistance increased in the mesenteric and renal regions and declined in the iliac (hindlimb) region. After icv administration of alpha-helical CRF9-41, HR and MAP responses during TMX were significantly attenuated. In addition, TMX-induced elevations of estimated mesenteric vascular resistance and iliac blood flow velocity were blunted after CRF receptor blockade. These altered cardiovascular and hemodynamic responses were ultimately reflected in the animals' compromised ability to run. The results suggest that the central nervous system actions of endogenous CRF are necessary for the full expression of the cardiovascular adjustments to TMX in the conscious rat.

Preclinical Pharmacology of Ro 31–6930, a New Potassium Channel Opener

The present study compares the effects of Ro 31-6930, a novel potassium channel opener, with those of cromakalim and nitrendipine on blood pressure and other haemodynamic parameters. In conscious, spontaneously hypertensive rats (SHR) the oral dose of Ro 31-6930 for lowering blood pressure was 10 times lower than that of cromakalim and some 100 times lower than that of nitrendipine. In addition, the duration of antihypertensive activity of Ro 31-6930 was longer than that of cromakalim or nitrendipine. The tachycardia evoked by Ro 31-6930 and cromakalim was of shorter duration than the antihypertensive effect of either agent. In a repeat, once daily dosing experiment no tolerance was observed to the antihypertensive effect of Ro 31-6930 over a 22-day period. In conscious normotensive cats Ro 31-6930 was 10 times more potent than cromakalim and 1,000 times more potent than nitrendipine in reducing blood pressure. The duration of hypotensive activity was in excess of 5 h for each agent. In anaesthetised dogs all three agents reduced mean arterial pressure (MAP) and total peripheral resistance (TPR), while increasing cardiac output (CO) via a rise in stroke volume (SV). Both Ro 31-6930 and cromakalim significantly reduced femoral (FVR) and mesenteric vascular resistances (MVR), while only cromakalim reduced renal vascular resistance (RVR). Ro 31-6930 is a potent new antihypertensive agent that compares favourably with cromakalim and nitrendipine.

Effects of behavior and social condition on cardiovascular response to footshock stress

Rats were instrumented with arterial catheters and directional-pulsed Doppler flow probes for assessment of blood pressure, heart rate, and blood flow in the renal, mesenteric, and hindquarter vascular beds. Subjects were tested in an intermittent shock procedure under paired and isolated social conditions and the cardiovascular indices associated with first shock, prone immobile behavior, upright behavior, and boxing behavior were recorded. Both shock procedures resulted in increased heart rate, mesenteric resistance, and renal resistance, as well as decreased hindquarter resistance. Blood pressure response was variable. Social and behavioral conditions generally accounted for little variance in cardiovascular indices during the treatments. Blood pressure assessed 2.5 min after the last shock was significantly higher in the isolated shock condition. In the context of divergent results from previous research in the area, the current results are most consistent with the view that a similar form of cardiovascular adjustment is present under paired and isolated shock, but that under some conditions the presence of a conspecific or the opportunity to fight may attenuate cardiovascular response to shock.

Posterior hypothalamic influences on cardiovascular effects of aortic nerve stimulation.

The purpose of this study was to examine the influence of stimulation of the posterior hypothalamus on the baroreflex responses produced by stimulation of the aortic depressor nerve. Animals were initially anesthetized and implanted with a bipolar electrode in the posterior hypothalamus. Three to 5 days later, animals were anesthetized with urethan, and the left aortic depressor nerve was dissected and placed on a bipolar platinum-iridium electrode. The effects of electrical stimulation of the posterior hypothalamus (0, 160, and 280 microA) were examined in baroreflex-intact and acutely sinoaortic baroreceptor-denervated animals, and the responses to aortic nerve stimulation (2, 8, 16, and 32 Hz) were examined during each level of hypothalamic stimulation. The first set of experiments was performed in baroreceptor-intact animals; e.g., in animals with arterial baroreceptor inputs intact from both carotid sinus regions in addition to intact right aortic baroreceptor afferent pathways. In that group, stimulation of the posterior hypothalamus attenuated the bradycardia and depressor effects of aortic nerve stimulation. When influences from other baroreceptor inputs were removed with acute sinoaortic baroreceptor denervation, posterior hypothalamic stimulation interrupted the reflex bradycardia due to aortic nerve stimulation; however, the depressor response to aortic nerve stimulation was not attenuated. Similar to the arterial pressure response, hypothalamic stimulation did not attenuate the decreases in mesenteric and iliac vascular resistance produced by aortic nerve stimulation in the baroreflex-denervated group. We conclude that posterior hypothalamic stimulation attenuates baroreflex-mediated bradycardia but does not alter baroreflex control of arterial pressure and peripheral vascular resistance.

Differential systemic and regional hemodynamic profiles of four angiotensin-I converting-enzyme inhibitors in the rat

Angiotensin-converting enzyme (ACE) inhibitors decrease blood pressure by reducing systemic vascular resistance. That the peripheral vasodilating properties of ACE inhibitors might not be homogeneously distributed in all vascular beds and might differ from one drug to another has been investigated in the normotensive rat by the pulsed Doppler technique using the active components of four different ACE inhibitors: captopril, enalapril, perindopril, and ramipril. Systemic (cardiac output and blood pressure) and regional (kidney, mesentery, hindquarter) hemodynamic responses to saline or to cumulative bolus injections (0.01-1 mg/kg) of captopril, enalaprilat, perindoprilat, or ramiprilat were continuously monitored. The effects of successive bolus injections (0.3-300 ng/kg) of angiotensinII were also investigated. The four ACE inhibitors produced an almost complete blockade of plasma angiotensin-II converting-enzyme activity (83%, 100%, 100%, and 100%, respectively), induced dose-dependent decreases in mean blood pressure, did not significantly affect cardiac output, and reduced total peripheral and mesenteric vascular resistances to the same extent. Hindlimb vascular resistance was identically decreased, but to a lower extent than total peripheral resistance by enalaprilat, perindoprilat, and ramiprilat, whereas it was increased by captopril at low doses only. Renal resistance was markedly decreased by the four drugs, and especially by captopril. The decreasing rank order for ACE-inhibitor-induced vasodilation is exactly the same (renal greater than total peripheral = mesenteric greater than hindlimb vascular resistances) as that of angiotensin-H-induced regional vasoconstriction, indicating that the vasodilator properties of ACE inhibitors are mainly due to angiotensin-II vasomotor tone suppression. None of the investigated compounds significantly affected mesenteric and hindlimb blood flows, except captopril, which lowered the latter significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional hemodynamic and baroreflex effects of endothelin in rats.

Endothelin is a peptide with potent, long-lasting pressor effects characterized by increases in mesenteric and hindquarters vascular resistance and bradycardia following an initial, transient depressor response. This study examined the mechanisms of action of endothelin on regional hemodynamics in conscious, freely moving rats and on baroreflex sensitivity both in conscious and chloralose-anesthetized rats. The pressor response to endothelin (0.67 nmol/kg) was attenuated by nifedipine (25 micrograms/kg) and augmented by chloralose anesthesia. The bradycardia was attenuated by pentolinium (10 mg/kg), atropine methyl sulfate (0.5 mg/kg), or chloralose anesthesia. Hindquarter vaso-constriction was attenuated by nifedipine, pentolinium, and atropine, whereas mesenteric vasoconstriction was less sensitive to blockade. The vasopressin V1 antagonist, [d(CH2)5Tyr(Me)]-AVP (20 micrograms/kg), indomethacin (5 mg/kg), or verapamil (150 micrograms/kg) did not affect any of these cardiovascular responses. Renal sympathetic nerve activity was reduced similarly in chloralose-anesthetized rats to pressor responses elicited by either phenylephrine or endothelin, and the slope of the baro-reflex function curve after endothelin was similar to that of phenylephrine. These results suggest that endothelin is a potent vasoconstrictor in which its action on visceral and skeletal muscle vasculature is mediated by somewhat different mechanisms. Endothelin does not alter baroreceptor reflex control of sympathetic nerve activity or heart rate.

Effects of intravenous AVP on cardiac output, mesenteric hemodynamics, and splanchnic nerve activity.

To elucidate the effects of intravenous arginine vasopressin (AVP) on the neural control of the circulation, we investigated the action of AVP on neural circulatory control with respect to its influence on cardiac output (CO), mesenteric blood flow (MBF), and splanchnic nerve activity (SpNA) in conscious rats. We implanted Doppler flow probes and bipolar electrodes into seven Wistar rats for continuous monitoring of CO, MBF, and SpNa. After the infusion of four different equipressor doses of AVP and methoxamine, the decreases in heart rate (HR) and CO were significantly greater with AVP than with methoxamine. Pretreatment with atenolol and methscopolamine bromide abolished the decreases in HR after both AVP and methoxamine injections but attenuated the AVP-induced decreases in CO less than the methoxamine-induced CO decreases. In untreated rats and in rats receiving cardiac autonomic blockade, the reduction in MBF and the increases in mesenteric resistance were greater after AVP than after methoxamine. Furthermore, SpNA decreased to a greater extent with all doses of AVP than with methoxamine. We conclude that in the rat the exaggerated reduction in CO induced by circulating AVP is not because of a sensitization of neural mechanisms but rather to caridac actions of the peptide. In contrast, AVP sensitizes the sympathetic control of the mesenteric vascular bed to counterbalance its potent local vasoconstrictor effects.

Effects of neuropeptide Y on the renal, mesenteric and hindlimb vascular beds of the conscious rabbit

The effects of neuropeptide Y (NPY, 10 μg/kg bolus i.v.) on renal, mesenteric and hindlimb blood flow were determined in intact conscious rabbits with chronically implanted Doppler ultrasonic flow transducers. The role of sympathetic neuro-effectors was assessed using inhibition of peripheral α-adrenoceptors with phentolamine in each group, and in the renal flow group following chemical sympathectomy with 6-hydroxydopamine. In controls, NPY caused markedly non-uniform peak responses. Renal blood flow fell from 2.16 ± 0.12 kHz to a minimum of 0.26 ± 0.07 kHz following NPY administration ( P < 0.05). Mesenteric blood flow was reduced from 2.04 ± 1.17 to 1.54 ± 0.11 kHz ( P < 0.05). Hindlimb blood flow increased transiently from 2.33 ± 0.15 to a peak of 3.33 ± 0.19 kHz ( P < 0.05). Renal vascular resistance rose by 1189 ± 309% and mesenteric resistance by 54 ± 9% ( P < 0.05), while hindlimb resistance fell by 24 ± 3% ( P < 0.05). Pretreatment with phentolamine accentuated the peak pressor response and the reduction in heart rate induced by NPY administration but had little effect on the local haemodynamic changes in each vascular bed. There was no change in the renal vascular response to NPY following sympathectomy. Indeed, the peak NPY-induced reduction in renal blood flow seen in control animals (87 ± 4%) was unaffected by either α-adrenoceptor inhibition (90 ± 5%) or by sympathectomy (86 ± 5%). In conscious rabbits with intact cardiovascular reflexes, pharmacological doses of NPY cause profound renal vasoconstriction with smaller changes in mesenteric and hindlimb flow. The effects of NPY on peripheral vascular tone are not mediated by sympathetic neuro-effectors.

Effects of PAF and BN 52021 on cardiac function and regional blood flow in conscious rats

The effect of intravenous injections (0.1-3 nmol/kg) of platelet-activating factor (PAF) on blood pressure, heart rate, cardiac output, and blood flow (hindquarter, renal, mesenteric) were studied in conscious rats. PAF decreased blood pressure and total peripheral resistance (TPR) but increased heart rate; cardiac output was reduced by the highest dose. Low doses of PAF increased blood flow and decreased vascular resistance in all vascular beds, whereas high doses reduced mesenteric blood flow in part by increasing mesenteric vascular resistance. The hypotensive and cardiac effects of PAF were blocked by intravenous infusions of the selective PAF-receptor antagonists, 15 mg/kg BN 52021 and 1 mg/kg SDZ 63-441. BN 52021 also attenuated the hindquarter and renal responses to PAF, but the mesenteric responses remained relatively unchanged. The results indicate that PAF is a potent vasodilator of mesenteric greater than hindquarter = renal vessels at low doses and a cardiac depressant at high doses. A therapeutic role for the PAF antagonists BN 52021 and SDZ 63-441 is suggested in endotoxemia, anaphylaxis, and other disease states in which increased release of PAF contributes to key hemodynamic derangements.

Central nervous system actions of corticotropin-releasing factor on cardiovascular function in the absence of locomotor activity

Studies were performed in conscious and anesthetized Sprague-Dawley rats to examine whether the cardiovascular responses to intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) required concomitant locomotor activation. I.c.v. administration of CRF to conscious animals elicited significant increases in arterial pressure, heart rate, mesenteric resistance, and iliac blood flow, as well as intermittent locomotor, grooming and chewing activity. Intravenous infusion of the anesthetic agent, Saffan, at the minimal dose required to abolish locomotor activity caused slight but significant elevations of heart rate and mesenteric vascular resistance. I.c.v. administration of CRF to anesthetized animals produced delayed, yet significant and sustained increases in the heart rate and arterial pressure, without altering regional blood flow. These results demonstrate that locomotor activation is not requisite for the expression of CRF-induced pressor and tachycardic responses. It is concluded that CRF acts within the central nervous system to influence cardiovascular function in the absence of locomotor activity.

Regional haemodynamic effects of vasopressin infusion in conscious, unrestrained, Brattleboro rats

1. Incremental rates of infusion (0.027-4.0 pmol min-1) of exogenous vasopressin were given for 10 min periods to conscious, Brattleboro (i.e. vasopressin-deficient) rats, which had been chronically instrumented with pulsed Doppler probes and intravascular catheters (to permit assessment of regional haemodynamic changes). 2. There were no significant effects of the two lowest rates of infusion (0.027 and 0.105 pmol min-1) but, after 10 min of vasopressin infusion at 0.313 pmol min-1, superior mesenteric vasoconstriction had occurred unaccompanied by any other changes. Infusion of vasopressin at 0.687 pmol min-1 produced increases in blood pressure and in both mesenteric and hindquarters vascular resistance, but not change in renal vascular resistance or heart rate. These results do not indicate specific interactions between exogenous vasopressin and baroreflex mechanisms to offset the pressor effect of the neuropeptide. 3. The marked bradycardia, hypertension and renal, mesenteric and hindquarters vasoconstriction seen after 10 min infusion of vasopressin at 4.0 pmol min-1 were all abolished 10 min after administration of an antagonist of V1-receptors [+)-(CH2)5Tyr(Et)DAVP); additional antagonism of V2-receptors (with the non-selective antagonist (+)-(CH2)5Tyr(Et)VAVP) had no effects on any measured variable. Hence, the present experiments provide no evidence for important vasodilator effect of vasopressin in conscious, Brattleboro rats.

Circulatory responses to heat after celiac ganglionectomy or adrenal demedullation.

Chloraloseanesthetized rats were implanted with Doppler flow probes on the mesenteric, renal, and external caudal arteries and were exposed to an ambient temperature of 40 degrees C. Heart rate, core (Tc) and tail-skin temperatures, and mean arterial blood pressure (MAP) were also monitored. Before heating, the celiac ganglion was removed (ganglionectomy) from one group of animals (n = 11) and a bilateral adrenal demedullation was performed in a second group (n = 14). As Tc progressively increased from 37 degrees C to 43 degrees C, MAP rose to a plateau then fell precipitously as Tc exceeded 41 degrees C. Ganglionectomy eliminated the rise in mesenteric resistance (P less than 0.05) and attenuated the rise in MAP compared with an intact control group (n = 11). Ganglionectomy also increased the heating rate (P less than 0.05) and reduced heat tolerance time (P less than 0.05). Demedullation attenuated the rise in both mesenteric resistance and MAP (P less than 0.05) and increased the rate of heating (P less than 0.05) compared with controls (n = 10). Renal and caudal resistance changes were similar in all groups. These data show the importance of intact adrenal medullas and sympathetic innervation to the splanchnic region in contributing to thermal tolerance in the rat. However, neither factor alone can explain splanchnic vasoconstriction during severe heat stress.

Effects of althesin and urethan-chloralose on neurohumoral cardiovascular regulation

The cardiovascular effects of althesin (ALT) and urethan-chloralose (UC) anesthesia were compared in conscious, chronically instrumented rats. Althesin had no effect on arterial pressure or base-line resistance in the renal, superior mesenteric, and hindquarters vasculatures but increased heart rate. In contrast, UC decreased arterial pressure, heart rate, and mesenteric resistance. Although UC attenuated depressor responses to nitroglycerin, neither anesthetic significantly altered regional vascular reactivity to intravenous phenylephrine and nitroglycerin. The cardiac chronotropic baroreflex was examined by comparing the slope of the curves relating maximal changes (delta) in heart rate (pulse interval) that occurred at the point coinciding in time with the maximal changes in mean arterial pressure produced by phenylephrine and nitroglycerin. Neither anesthetic significantly altered the baroreflex slope (delta pulse interval/delta mean arterial pressure) for pressor and depressor stimuli. Both anesthetics attenuated the sympathoexcitatory response to cerebroventricular angiotensin II, although ALT had less of a depressive effect (pressor response during ALT and UC = 65 and 30%, respectively, of conscious). Plasma renin activity (PRA) and the hemodynamic response to peripheral angiotensin-receptor antagonism were significantly increased (PRA by almost 6-fold) during UC, whereas ALT was without effect. Similarly, UC but not ALT induced vasopressin-dependent vascular tone. Ganglionic blockade indicated that peripheral neurogenic tone was not altered by ALT anesthesia. These data suggest that althesin produces fewer hemodynamic disturbances than urethan-chloralose and largely maintains cardiovascular regulation intact.

Effect of hindlimb suspension on VO2 max and regional blood flow responses to exercise.

Male rodents were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDT). Testing included measurements of maximal O2 uptake (VO2 max) and select cardiovascular responses to graded treadmill exercise. VO2 max expressed on an absolute basis (ml/min) was significantly decreased after HOZ (-14.1 +/- 2.5%) and HDT (-14.3 +/- 2.0%), while being essentially unchanged in CON (-1.0 +/- 3.3%). Significant reductions in body weight were observed after both HOZ (-10.1 +/- 4.2 g) and HDT (-22.5 +/- 3.3 g), whereas CON animals exhibited a significant increase in weight (10.4 +/- 3.8 g). As a result, when VO2 max was normalized for body weight, all groups exhibited similar significant reductions of 6-7%. Although no differences in heart rate and blood pressure response to graded exercise were observed, the HDT group exhibited greater increases in mesenteric resistance at the same absolute exercise intensity. Furthermore, both suspended groups had higher iliac resistance values during exercise at similar relative exercise conditions, suggesting that muscle blood flow during treadmill running may have been reduced after suspension. In general, the decrements associated with the HOZ and HDT conditions were similar. It was concluded that reduction in exercise capacity and altered cardiovascular responses to exercise observed after 6-9 days of suspension were attributable to a combination of hypokinesia, lack of hindlimb weight bearing, or restraint, rather than to hydrostatic influences associated with HDT.