Hindlimb Vascular Resistance Research Articles

Effects of coronary occlusion on arterial baroreflex control of heart rate and vascular resistance.

This study was planned to assess whether circumflex coronary occlusion (CO) impairs the arterial baroreflex control of heart rate (HR) and hindlimb vascular resistance (HVR), and to determine the mechanisms involved in the mediation of these phenomena. Increasing doses of phenylephrine and nitroglycerin were given intravenously to anesthetized dogs with a constant flow-perfused hindlimb before and during 30-s CO. The reflex responses were assessed by the changes in HR and hindlimb perfusion pressure evoked by changes in arterial pressure following phenylephrine and nitroglycerin administration. During CO, there was an attenuation of the reflex control of HR and HVR as compared with control conditions. The application of lidocaine on the left ventricular epicardial surface was able to prevent the effect of CO on both the baroreflex responses. The intravenous administration of atropine prevented only the impairment in arterial baroreflex control of HR induced by CO. After the injection of phentolamine into the perfused hindlimb, the baroreflex had no effect on HVR either before or during CO. Finally, intravenous administration of propranolol failed to modify the effect of CO on both the baroreflex responses. These data indicate that CO attenuates the arterial baroreflex control of both HR and HVR through the stimulation of left ventricular receptors. The effect on HR is mediated by the parasympathetic system, whereas the effect on HVR is due to sympathetic efferents.

The role of alpha-adrenergic receptors in carbon monoxide hypoxia.

The importance of alpha-adrenergic receptors in the cardiac output and peripheral circulatory responses to carbon monoxide (CO) hypoxia was studied in anesthetized dogs. Phenoxybenzamine (3 mg/kg i.v.) was injected to block alpha-receptor activity and the data obtained were then compared with those from a previous study of CO hypoxia in unblocked animals. Values for cardiac output, hindlimb blood flow, vascular resistance, and oxygen uptake were obtained prior to and at 30 and 60 min of CO hypoxia which reduced arterial oxygen content by approximately 50%. alpha-Adrenergic blockade resulted in a lower (p less than 0.05) control value for cardiac output than observed in unblocked animals, but no differences were present between the two groups at 30 or 60 min of CO hypoxia. Similarly, limb blood flow was lower (p less than 0.05) during the control period in the alpha-blocked group but rose to the same level as that in the unblocked animals at 60 min of COH. No change in limb blood flow occurred during CO hypoxia in the unblocked group. These findings demonstrated that during CO hypoxia alpha-receptor mediated venoconstriction does not contribute to the cardiac output response and alpha-receptor mediated vasoconstriction probably does prevent a rise in hindlimb skeletal muscle blood flow.

Effects of hypertension and hypercholesterolemia on vasodilatation in the rabbit.

Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1% cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemic responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia.

Neural effects of systemic hypoxia and hypercapnia on hindlimb vascular resistance in acute spinal cats.

The effects of systemic hypoxia and hypercapnia on the neurogenic component of hindlimb vascular resistance were studied in 10 unanesthetized acute Cl spinal cats. Hindlimb perfusion pressure (PP) was measured under conditions of constant flow of normoxic and normocapnic blood from a donor cat. Ventilation with 5% CO2 and 10% CO2 in O2 caused increases in PP of 15 +/- 2 (mean +/- SE) mm Hg and 27 +/- 3 mm Hg from a control level of 106 +/- 6 mm Hg during ventilation with 100% O2. Changing the inspired gas mixture from 95% O2 plus 5% CO2 to 12.5%, 10%, 7.5%, or 5% O2 plus 5% CO2 in N2 caused increases in PP of 1.5 +/- 1, 14 +/- 2, 38 +/- 6, and 69 +/- 15 mm Hg respectively from a control level of 121 +/- 9 mm Hg. These vasoconstrictor effects were abolished by ganglionic blockade with hexamethonium (10 mg/kg iv). We conclude that in the acute Cl spinal cat a large part of the population of sympathetic preganglionic neurons in the lumbar spinal cord, controlling vascular smooth muscle of the hindlimb, is excited by systemic hypoxia or hypercapnia over a considerable range of PaO2 and PaCO2 values.

Endothelium-dependent relaxation is unaltered by hypertension, cholesterol or intimal thickening.

The effect of cellophane wrap hypertension (WRAP) and hypercholesterolemia (1% cholesterol diet, CHOL) for 4 weeks was assessed on the endothelium-dependent vasodilator response to acetylcholine in conscious rabbits after pharmacological autonomic blockade. Dose-response curves for the hindlimb vascular resistance (ear artery pressure/lower aortic blood flow; Doppler flowmeter) and acetylcholine infusion (i.v.) doses were unaltered in sensitivity (ED50) for any of the treatment groups. The range and slope of the curves were significantly altered by WRAP, CHOL or WRAP plus CHOL for acetylcholine and adenosine infusions consistent with medial hypertrophy in resistance vessels and raised serum viscosity. The effect of intimal thickening on the response to endothelium derived relaxing factor (EDRF) was tested in dog carotid artery ring segments in vitro 4 weeks after endothelium removal. The relaxation responses to acetylcholine (EDRF-dependent) and adenosine or nitroglycerin were not significantly altered by the neo-intima. Therefore the response to EDRF released by acetylcholine in resistance vessels was unaltered by hypertension, hypercholesterolemia or both together. Neo-intimal thickening in response to initial endothelium loss does not appear to alter EDRF responses in the carotid artery.

Perindopril, a New Converting Enzyme Inhibitor: Systemic and Regional Hemodynamics and Sympathoinhibitory Effects in Spontaneously Hypertensive Rats

The effects of a new converting enzyme inhibitor, perindopril (5 mg/kg p.o. q.d. for 8 days), on systemic and regional hemodynamics, as well as its interferences with the sympathetic nervous system at the cardiovascular level, were investigated in nonbinephrectomized and in binephrectomized spontaneously hypertensive rats (SHRs). Perindopril abolished plasma converting enzyme activity and lowered arterial blood pressure (BP) without affecting heart rate. Cardiac index (microspheres) was not drug affected; thus, the reduction in BP was due to a decrease in total peripheral resistance which was shown to be homogenous, since all investigated vascular resistances were reduced to the same extent. In nonbinephrectomized, pithed SHRs, perindopril decreased BP and renal and hindlimb vascular resistances (pulsed Doppler). In addition, perindopril exerted a sympathoinhibitory effect as evidenced by (a) a reduction in the systemic vasopressor and regional vasoconstrictor responses to the alpha 1-adrenoceptor agonist, cirazoline, and especially to the alpha 2-adrenoceptor agonist UK 14.304; and (b) a decrease in the systemic pressor and in the hindlimb vasoconstrictor responses to spinal cord stimulation. In binephrectomized, pithed SHRs, perindopril no longer decreased BP; however, whereas its sympathoinhibitory effect versus alpha-adrenoceptor agonists was abolished, that versus spinal cord stimulation persisted. These results indicate that (a) perindopril lowers BP in SHRs by a renal-dependent mechanism; (b) perindopril exerts in SHRs a sympathoinhibitory effect versus alpha-adrenoceptor agonists and spinal cord stimulation; (c) the sympathoinhibitory effect of perindopril versus alpha-adrenoceptor agonists is postjunctional and kidney dependent; and (d) the sympathoinhibitory effect of perindopril versus spinal cord stimulation is possibly prejunctional in its mechanism and does not require the presence of the kidneys.

The effect of pregnancy on the changes in hind-limb vascular resistance following haemorrhage in the rabbit.

The change in vascular resistance of the skinned hind limb perfused at constant flow has been measured following rapid removal of 10% of the blood volume in anaesthetized pregnant rabbits (27-29 days gestation) and compared with that of non-pregnant rabbits. 5 s after haemorrhage was completed vascular resistance had risen in all rabbits, but in the pregnant ones this increase was only one-fifth of that in the non-pregnant ones. After section of either the carotid sinus and aortic nerves or the sympathetic innervation to the hind limb the increases of vascular resistance at this time were abolished. It is concluded that the previously described diminution during pregnancy of the protective function of the baroreflexes during haemorrhage results, to some extent, from their diminished role in a vascular bed not associated with the reproductive process. The blood withdrawn was not re-infused for 10 min, throughout which, in all rabbits with sinus, aortic and sympathetic nerves intact, the increase in vascular resistance was sustained. After section of the carotid sinus and aortic nerves and the sympathetic innervation there was, during this 10 min, a slow increase in vascular resistance comparable in final size to that which occurred immediately in the respective innervated preparations, i.e. it was smaller in the pregnant than in the non-pregnant rabbits. A possible difference in action during pregnancy of a vasoconstrictor substance released during haemorrhage is discussed briefly.

The role aortic chemoreceptors during severe CO hypoxia.

The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached.

Reflex depression of cardiovascular function during lung inflation.

These experiments were intended 1) to determine the cardiovascular reflex response initiated by lung inflation and 2) to determine the autonomic neural mechanisms that mediate the reflex responses. To test only the reflex effects of lung inflation and eliminate the associated mechanical effects thereof, we isolated the left airway and left pulmonary artery of dogs and performed static inflations of the left lung. Left lung inflation (LLI) to 30 cmH2O caused left ventricular systolic pressure, heart rate, and hindlimb vascular resistance to fall 20, 31, and 15%, respectively. When the hearts were paced to eliminate Bowditch effects, LLI caused left ventricular contractility, which was measured as dP/dt at 30 mmHg developed pressure and as the maximal rate of shortening of the contractile element, to fall 23 and 20%, respectively, and cardiac output (stroke volume) to fall 31%. Transection of the left cervical vagus nerve, interrupting most afferent and some efferent pathways from the left lung, virtually eliminated subsequent cardiovascular responses to LLI. Hindlimb vasodilation was mediated by alpha-adrenergic activity, and the fall in left ventricular contractile state was caused by a reduction in beta-adrenergic activity. The reflex bradycardia was mediated by increased cholinergic and decreased beta-adrenergic activity. These data establish that reflex mechanisms exist whereby expansion of the lung can reflexly modulate heart rate, ventricular contractility, systemic vasomotor tone, cardiac output, and stroke volume independent of the direct mechanical influence of lung expansion on these circulatory phenomena.

Altered control of hindlimb vascular resistance by vagal afferents in spontaneously hypertensive rats. Difference in the early and late stage of hypertension.

The aim of this study was to examine whether control of vascular resistance by vagal afferents is altered in the early as well as late stage of hypertension. We examined the effects of vagotomy on hindlimb vascular resistance as well as on arterial baroreflex control of hindlimb vascular resistance in spontaneously hypertensive rats and Wistar-Kyoto rats, 12 and 35 weeks old. Vagotomy in rats with the intact arterial baroreceptors increased hindlimb vascular resistance in all four groups. Hindlimb vascular responses to graded sympathetic nerve stimulation were closely linear up to 6 Hz in all groups, and the slope of the response was approximately 1.4 times steeper in spontaneously hypertensive than in Wistar-Kyoto rats, in both the young and old groups. The increase in hindlimb vascular resistance after vagotomy normalized by the slope of the response to sympathetic nerve stimulation was greater in young spontaneously hypertensive rats than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive rats than in old Wistar-Kyoto rats. Vagotomy increased the gain of arterial baroreflex control of hindlimb vascular resistance in young spontaneously hypertensive rats, and in two groups of Wistar-Kyoto rats, but not in old spontaneously hypertensive rats. The percent increase in the gain of arterial baroreflex control of hindlimb vascular resistance after vagotomy tended to be greater in young spontaneously hypertensive than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. Central venous pressure and left ventricular end-diastolic pressure were higher in spontaneously hypertensive than in Wistar-Kyoto rats in both young and old groups. Left atrial distensibility assessed by obtaining the atrial pressure-volume relationship was comparable between young spontaneously hypertensive and young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. These results indicate that vagal afferents exert tonic inhibition on control of hindlimb vascular resistance in spontaneously hypertensive as well as in Wistar-Kyoto rats, and that tonic inhibitory influence of vagal afferents on control of hindlimb vascular resistance is altered in spontaneously hypertensive rats, augmented in young, but attenuated in old, spontaneously hypertensive rats, compared with that in age-matched Wistar-Kyoto rats. It is considered that altered control of vascular resistance by vagal afferents in spontaneously hypertensive rats may result from changes in vagal afferent activity.

Influence of captopril and enalapril on regional vascular alpha-adrenergic receptor reactivity in SHR.

The effects of short-term oral treatment with captopril and enalapril (two angiotensin-I-converting-enzyme inhibitors [ACEIs] that were administered in equipotent antihypertensive doses) on the systemic vasopressor response and on the renal, mesenteric, and hindlimb vascular responses to cirazoline and UK-14,304 (alpha 1- and alpha 2-adrenergic receptor-specific agonists, respectively) were investigated in adult pithed spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain. In the nonbinephrectomized animal, captopril and enalapril reduced to the same extent the systemic blood pressure and renal and hindlimb vascular resistances. They also decreased to the same extent systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304, especially in the renal and mesenteric vascular beds. Simultaneously, the effects of angiotensin I and angiotensin II on the pressor response were abolished and almost not modified. In the binephrectomized animals, captopril and enalapril no longer reduced the systemic blood pressure and regional vascular resistances, but whereas the sympathoinhibitory effect of captopril vs the systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304 persisted, those of enalapril disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural effects of systemic hypoxia on hindlimb vascular resistance in sinoaortic-denervated cats

The effects of systemic hypoxia on the neurogenic component of hindlimb vascular resistance were studied in six sinoaortic-denervated, anesthetized cats with intact central nervous system. Hindlimb perfusion pressure (PP) was measured under conditions of constant flow of normoxic blood from a donor cat. The neural component of the PP was estimated from the change in PP upon administration of hexamethonium (10 mg/kg i.v.). Ventilation of the recipient cat with 12.5% and 10% O2 was associated with an average 35 +/- 15% (SEM) and 13 +/- 10% decrease, respectively, of the estimated neural component of the PP. In contrast ventilation with 7.5% and 5% O2 produced increases of 27 +/- 7% and 58 +/- 10%, respectively, of the estimated neural component of the PP. Both the vasodilator and vasoconstrictor responses were abolished by hexamethonium (10 mg/kg i.v.). The vasodilator response appeared to be due to withdrawal of alpha-adrenergic tone since it was eliminated by constant infusion of phentolamine to the hindlimb (45 micrograms/ml blood/min). We conclude that, in addition to the already known sympatho-excitation seen in the sinoaortic-denervated cat during severe systemic hypoxia, there is also a sympatho-depressant effect which dominates at more moderate levels of systemic hypoxia.

Cardiovascular pharmacology of ACC-9089--a novel, ultra-short-acting, beta-adrenergic receptor antagonist.

The beta-adrenergic receptor blocking properties of ACC-9089 were studied in isolated cardiac and tracheal tissues from guinea pigs and in anesthetized dogs. The compound was a potent, nonselective beta-blocker in isolated tissues (atrial pA2 8.01; tracheal pA2 8.16). ACC-9089 was without intrinsic sympathomimetic action and caused direct cardiac depression only at concentrations that were four orders of magnitude higher than its pA2. In anesthetized dogs, ACC-9089 produced steady-state beta-blockade within 20 min of initiation of 3-h intravenous infusions. Recovery from beta-blockade occurred rapidly following termination of infusion (80% recovery in 17 +/- 2 min after 1.2 microgram/kg/min). Intravenous infusion of ACC-9089 caused dose-dependent inhibition of heart rate responses to sympathetic nerve stimulation and inhibition of isoproterenol-induced decreases in perfusion pressure in a perfused hindlimb preparation. The compound (a) did not produce alpha-blockade; (b) had no direct effect on hindlimb vascular resistance; and (c) did not alter hemodynamic variables in catecholamine-depleted dogs. The results indicate that ACC-9089 is a novel, ultra-short-acting beta-blocker that does not possess direct cardiovascular effects beyond those expected as a result of beta-blockade.

Occlusive summation of carotid and aortic baroreflexes in control of renal nerve activity.

We recently reported that denervation of aortic or carotid baroreceptors impaired baroreflex control of heart rate but not of hindlimb vascular resistance or lumbar sympathetic nerve activity. Since baroreflex control of sympathetic outflow to different vascular beds is nonuniform, we determined whether carotid or aortic baroreceptor denervation would impair baroreflex control of renal nerve activity. Experiments were performed in 23 alpha-chloralose-anesthetized rabbits. Phenylephrine and nitroglycerin were infused to raise or lower arterial pressure. Pressure elevation inhibited and pressure reduction increased renal nerve activity. The linear regression relationships between changes in arterial pressure and percent change in renal nerve activity were determined with baroreflexes intact and after aortic or carotid denervation. Neither carotid nor aortic denervation alone impaired baroreflex control of renal nerve activity. In nine experiments responses were determined first with vagi sectioned. The results were comparable to those obtained without prior vagotomy. Our data indicate that one group of baroreceptors (aortic or carotid) exerts full control of renal nerve activity and that aortic and carotid baroreflex influences on renal nerve activity add by occlusive or mutual inhibitory summation.

Blockade of GABA receptors in periventricular forebrain of anesthetized cats: Effects on heart rate, arterial pressure, and hindlimb vascular resistance

Pharmacologic antagonism of GABAergic inhibition in the periventricular forebrain of anesthetized cats caused dose related (1) sympathetically mediated increases in heart rate and arterial pressure in vagotomized cats, and (2) suppression of reflex vagal activation in vagus-intact preparations where sympathetic effects are prevented by cervical spinal cord transection. In the present study performed in cats with intact autonomic pathways, similar administration of the GABA antagonist bicuculline methiodide (BMI) produced dose-related increases in arterial pressure, heart rate, and, when perfusion pressure in the autoperfused hindlimb was measured, vascular resistance. Furthermore, the relationship between heart rate and hindlimb vascular resistance changes suggested that the effects on heart rate reflected the combined sympathetic and vagal baroreflex effects of BMI. Intraventricular administration of muscimol, a potent GABA agonist, elicited abrupt and parallel reversal of BMI-induced effects on systemic arterial pressure and vascular resistance while attempts to acutely denervate the hindlimb at the height of the BMI response by cutting the femoral and sciatic nerves sharply reversed the increase in hindlimb vascular resistance in most experiments. The results suggest that the cardiovascular changes observed represent an integrated pattern consisting of excitation of sympathetic nerves innervating the heart and vasculature along with suppression of reflex evoked vagal excitability.

Impaired baroreflex control of vascular resistance in prehypertensive Dahl S rats

The purpose of this study was to examine baroreflex control of vascular resistance and heart rate in prehypertensive Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Urethan-anesthetized normotensive DS rats demonstrated significantly impaired baroreflex control of both hindlimb vascular resistance and heart rate. This impairment was not secondary to elevated arterial pressure since blood pressure did not differ between DR and DS rats fed a low sodium diet. Vascular baroreflex responses were shown to depend on the integrity of efferent sympathetic innervation and to be mediated by the sinoaortic afferent arterial baroreceptors. No strain difference was observed for hindlimb vasodilation produced by papaverine or graded doses of nitroprusside, indicating that differences in resistance vessel vasodilator capacity or responsiveness could not account for differences in baroreflex responses. Since impaired baroreflex control was evident in DS rats prior to any elevation in arterial pressure, this abnormality may contribute to the DS rat's genetic propensity to develop hypertension.

Diving responses in ducks after acute barodenervation.

The contribution of systemic arterial baroreceptors to the cardiovascular adjustments to diving has been investigated in unanesthetized ducks after acute baroreceptor denervation. Both intact and denervated ducks exhibited bradycardia on diving, although denervated ducks showed a lesser and more variable fall in heart rate. Hindlimb vascular resistance rose significantly in both intact and denervated ducks. Continuous stimulation of one depressor nerve, through miniature electrodes implanted on the cut central end, resulted in a diving bradycardia intermediate between that recorded in intact and denervated animals. Intermittent stimulation of the depressor nerve, for 20-s periods, at intensities high enough to cause a large fall in mean arterial pressure (MAP) predive caused a smaller reduction in MAP as a dive was prolonged, due to a large decline in the ability of the baroreceptor reflex to affect peripheral resistance. There was no change in the effect of stimulation on cardiac control before or during diving. The present experiments indicate that a barostatic reflex, which exerts its effects primarily through cardiac control and not control of total peripheral resistance, is active through the dive but that the majority of the diving response in ducks is independent of baroreceptor integrity.

Reflex control of arterial compliance in rabbits.

Reflex control of arterial compliance of the hind limb circulation has been assessed in rabbits. Brief interruption of constant flow perfusion of the hind limb produced a pressure decay that was determined by hind limb vascular resistance and arterial compliance; thus independent assessment of resistance was used to derive compliance. Experiments were performed under control conditions, during baroreceptor deactivation and during stimulation of water-sensitive receptors in the upper respiratory airways. Hind limb vascular resistance increased by more than 80% when either reflex was elicited, but parallel changes in the pressure decay curves were not observed. Instead a decrease in arterial compliance compensated for the elevation in vascular resistance. These results indicate that the dynamic elastic properties of the arterial tree can be reflexly controlled such that the time course of adjustments of arterial pressure is relatively independent of vascular resistance.

Role of central and peripheral chemoreceptors in diving responses of ducks.

Using techniques of vascular isolation and subsequent perfusion we have investigated the effects of altering blood gas tensions, in the cerebral and carotid body circulations, on some cardiovascular responses to diving in unanesthetized ducks. After denervating the right carotid body, perfusion of the innervated left carotid body with hyperoxic blood significantly reduced diving bradycardia and reduced the increase in hindlimb vascular resistance (HLVR) in 1-min dives compared with dives in which the innervated carotid body was autoperfused. Denervation of systemic arterial baroreceptors reduced the fall in heart rate (HR) and increased the rise in HLVR in all dives. Cross-perfusion of the head, from a donor with blood of normal blood gas tensions, did not significantly affect HR or HLVR in 2-min dives compared with dives in which the head was autoperfused. however, cross-perfusing the cerebral circulation with blood of elevated PaCO2 caused significantly greater increases in HLVR than when high PaCO2 only affected the peripheral circulation. We conclude that peripheral chemoreceptors cause virtually all the bradycardia in the later stages of a dive but only about one-half the increase in HLVR, a significant contribution comes from the stimulation of central chemoreceptors with blood of high PaCO2.

Total and hindlimb O2 uptake and blood flow in hypoxic dogs given dopamine.

Cardiovascular interactions between dopamine and hypoxia were examined in 8 anesthetized, paralyzed dogs ventilated at constant rates. Total and hindlimb (less paw) O2 uptake, blood flow, and vascular resistance were measured with and without dopamine infusion of 10 micrograms/kg . min during both normoxic and hypoxic ventilation. Another 8 dogs were similarly treated after beta-blockade with propranolol infusion (1 mg/kg). During the baseline period, normoxic dopamine significantly increased total O2 uptake, cardiac output, and stroke volume, and significantly decreased total vascular resistance in the control group. Hypoxia decreased total O2 uptake, cardiac output, and heart rate but increased total vascular resistance. Dopamine reversed each of these hypoxic changes and restored total O2 uptake to normoxic levels. Hindlimb measurements were not significantly changed by dopamine or hypoxia in the control group. During hypoxia, beta-blockade abolished dopamine's effects except for the decrease in total vascular resistance. The improvement in cardiac output and O2 transport by dopamine infusion resulted from increased stroke volume during normoxia and from increased heart rate during hypoxia.