Effects of compartmental fluid repletion on heat-induced limb vasodilation in dehydrated baboons.

Dehydration attenuates the increase in hindlimb blood flow produced by environmental heating (EH) in baboons. This study explored whether intravascular volume repletion alone was sufficient to remove this dehydration-induced attenuation. In six unanesthetized, chronically instrumented baboons, the increases in hindlimb blood flow during EH were measured under these conditions: euhydrated, dehydrated (64-68 h of water deprivation) without fluid replenishment, and dehydrated with intravenous fluid replenishment by either 6% high-molecular-weight dextran solution (to replenish vascular volume) or hyperosmotic saline (to replenish vascular and interstitial fluid volumes). EH consisted of acute exposure to ambient temperatures of 38-42 degrees C until core temperature (Tc) reached 39.5 degrees C. During dehydration without fluid replenishment the increments in mean iliac artery blood flow (MIBF) and iliac vascular conductance (IVC) produced by EH (i.e., value at Tc = 39.5 degrees C - pre-EH value) were reduced by 39 and 44%, respectively. After infusion of a volume of dextran solution equal to blood volume lost during dehydration, the increment in MIBF during EH was partially restored to the euhydrated level, but the increment in IVC remained at the dehydrated level. Infusion of hyperosmotic saline during dehydration completely restored the increases in MIBF and IVC during EH to euhydrated levels. Thus restoration of normal blood volume alone in dehydrated baboons does not completely restore normal hindlimb vasodilation during EH.

Effects of hyperosmolality and diuretics on heat-induced limb vasodilation in baboons.

Dehydration attenuates the increase in limb skin blood flow elicited by environmental heating (EH). This study sought to determine which of the two primary effects of dehydration, increased body fluid osmolality or decreased body fluid volume, was primarily responsible for this cutaneous vasoconstrictor bias in baboons. Unanesthetized chronically instrumented baboons were exposed to EH while in euhydrated state, after 65-69 h of water deprivation (dehydration), after infusion of a small volume of hypertonic (20%) saline to raise plasma osmolality and sodium concentration to dehydration levels, and after injections of the diuretic furosemide over a 64-h period to produce an isosmotic fall in extracellular fluid volume. EH consisted of an acute elevation of ambient temperature to 39.5-42.0 degrees C until internal temperature reached 39.5-39.8 degrees C. The normal increases in external iliac artery blood flow and iliac vascular conductance during EH were unchanged by hyperosmolality but were attenuated by 39 and 31%, respectively, after furosemide treatment and by 42 and 46%, respectively, during dehydration. Thus the fall in extracellular fluid volume is the component of dehydration that attenuates the increase in hindlimb blood flow during EH in the same way as dehydration itself.

Effect of water or saline intake on heat-induced limb vasodilation in dehydrated baboons.

Dehydration markedly attenuates the increase in hindlimb blood flow elicited by environmental heating (EH) in baboons. This study sought to determine the importance of gradually produced increases in body fluid osmolality and decreases in body fluid volume in producing this attenuation. The hindlimb blood flow increases during EH of seven unanesthetized chronically instrumented baboons were examined during euhydration, dehydration (64-68 h of water deprivation), and after ad libitum oral rehydration with either water or a hyperosmotic saline solution. EH consisted of acute exposure to ambient temperatures of 38-42 degrees C until internal temperature reached 39.5 degrees C. Dehydration depressed the maximal external iliac artery blood flow (MIBF) and iliac vascular conductance (IVC) attained during EH in the euhydrated state by 37 and 43%, respectively. Rehydration with either water or saline solution, however, restored maximal MIBF and IVC to euhydrated levels. Because plasma osmolality remained at dehydrated levels after rehydration with saline, hyperosmolality does not produce the dehydration-induced attenuation in hindlimb blood flow.

Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons.

This study primarily sought to determine whether the role of vasopressin (VP) in maintenance of arterial blood pressure is enhanced in awake, chronically instrumented baboons after 68-72 h of dehydration. This question was approached by pharmacologically blocking vasopressin V1-receptors in euhydrated and dehydrated baboons with or without a normally functioning renin-angiotensin system (RAS). VP blockade during dehydration produced a rapidly occurring (within 5 min), statistically significant (P less than 0.05) decrease in mean arterial pressure (MAP) of 5 +/- 1 mmHg in the RAS-intact condition and an identical decline in MAP (5 +/- 1 mmHg) during blockade of the RAS by captopril, an angiotensin I-converting enzyme inhibitor. At 15 min after induction of VP blockade, heart rate was elevated by 9 +/- 2 beats/min in the RAS-intact condition and by 20 +/- 5 beats/min in the RAS-blocked condition. In addition, VP blockade in the dehydrated state produced small and equal increases in hindlimb vascular conductance in RAS-intact and RAS-blocked conditions. None of these cardiovascular changes were produced by VP blockade in the euhydrated state. RAS blockade produced modest declines in MAP in both hydration states, but the fall was larger by 7 +/- 4 mmHg in the dehydrated state. Thus both VP and the RAS contribute to the maintenance of arterial blood pressure during dehydration in the conscious baboon.

Influence of dehydration on locally mediated hindlimb vasodilation in baboons.

Previous studies indicate that the heat stress-induced cutaneous vasodilation in baboons is attenuated during dehydration by mechanisms other than the well-known neurohumoral vasoconstrictor mechanisms. Therefore, this study sought to determine whether dehydration also attenuates locally mediated maximum hindlimb blood flow and vascular conductance in baboons. Five baboons were chronically instrumented to measure arterial blood pressure and mean external iliac artery blood flow (MIBF). Hindlimb vasodilation was induced by occlusions of the external iliac artery for 2.5, 5.0, 7.5, and 10.0 min and by close-arterial injections of acetylcholine (ACh) and sodium nitroprusside (NP) in graded doses. These vasodilatory stimuli were applied in euhydrated and dehydrated states, the latter being produced by water deprivation for 64-68 h. Maximum MIBF and iliac vascular conductance (IVC) after arterial occlusion were reduced by 67-70% during dehydration. Also, maximum MIBF and IVC produced by ACh in the dehydrated state were 46-52% lower than in the euhydrated state. A similar reduction in the responses to NP occurred during dehydration. It is concluded that the maximum hindlimb blood flow and vascular conductance produced by local, nonneurohumoral mechanisms are attenuated in the baboon during dehydration.

Influence of vasoconstrictor systems on leg vasodilation during heating of dehydrated baboons.

This study, carried out in two parts, sought to determine the importance of vasopressin (VP), the renin-angiotensin system (RAS), and the sympathetic nervous system in the dehydration-produced attenuation of hindlimb (cutaneous) vasodilation during environmental heating (EH). Baboons, chronically instrumented for blood sampling and for measurement of mean iliac blood flow (MIBF), arterial pressure, and core temperature (Tc), were subjected to EH while in euhydrated and dehydrated (64-72 h of water deprivation) states. EH consisted of exposure to an elevated ambient temperature (40-42 degrees C) until Tc reached 39.5 degrees C. In part I, indexes of the above vasoconstrictor systems were measured. Base-line plasma renin activity (PRA) and VP and norepinephrine concentrations were all significantly elevated by dehydration. In addition, the increase in PRA during EH was accentuated by dehydration. In part II, the effects of blockades of the RAS, the pressor action of VP, and the innervation of the hindlimb on hindlimb vasodilation during EH were assessed. None of these blockades, singly or together, reversed the dehydration-produced attenuation of the increase in MIBF during EH. Thus we conclude that other mechanisms are responsible for the dehydration-produced attenuation of cutaneous vasodilation in baboons during EH.

Control of plasma renin activity in heat-stressed baboons on varied salt intake.

The characteristics and control of the increase in plasma renin activity (PRA) during environmental heating (EH) were determined in 12 unanesthetized, chronically catheterized baboons. Each EH experiment consisted of a 1.5- to 4-h exposure to an ambient temperature of 39-44 degrees C until core temperature (Tc) reached 39.5-40.0 degrees C. These EH experiments were done on the baboon in an unblocked state and during beta-adrenergic receptor blockade produced by propranolol when on normal-to-high salt intake (NHSI) and on low-salt intake (LSI). PRA rose linearly with Tc during EH, but the increase in PRA was considerably larger when the baboon was on LSI. The PRA-Tc linear regression coefficients were 2.32 and 5.98 ng angiotensin I X ml-1 X h-1 X degrees C-1 in NHSI and LSI states, respectively. This rise in PRA during EH was completely eliminated during beta-blockade in both NHSI and LSI states. It is concluded that heat stress activates the sympathetic nervous system to stimulate beta-receptor-mediated renin secretion by the kidney, this activation is controlled primarily by internal thermoreceptors, and variations in salt intake alters only the magnitude of the increase in PRA during heat stress, not the mechanisms that produce it.

Effect of sodium depletion on peripheral vascular responses to heat stress in baboons.

The cutaneous vasodilation and renal vasoconstriction in baboons during environmental heating (EH) appear to be produced predominantly by sympathetic vasoconstrictor withdrawal and activation of the renin-angiotensin system, respectively. Since these mechanisms may be influenced differently by sodium depletion, this study examined the hypothesis that sodium depletion would have a differential effect on cutaneous and renal vascular responses to EH. Sodium depletion was produced in chronically instrumented baboons by placing them on low-salt intake for 8-19 days along with diuretic administration. EH consisted of exposing the baboon to an ambient temperature of 40-42 degrees C until core temperature (Tc) reached 39.8-40.0 degrees C. Both control plasma renin activity (PRA) and the rise in PRA with Tc during EH were considerably larger in sodium-depleted baboons. However, the magnitudes of the progressive increases in iliac vascular conductance (used as an index of hindlimb cutaneous vasodilation) and renal vascular resistance with rising Tc during EH were unaltered by sodium depletion. Therefore, neither cutaneous nor renal vascular responses to EH are influenced by elevated PRA and other changes accompanying sodium depletion in the baboon.

Attenuation of hindlimb vasodilation in heat-stressed baboons during dehydration.

The influence of dehydration on hindlimb vasodilation during environmental heating (EH) was examined in eight unanesthetized chronically instrumented baboons. Mean iliac blood flow (MIBF), arterial blood pressure, and core temperature (Tc) were measured during EH of baboons in euhydrated and dehydrated states. EH consisted of acute exposure to high ambient temperatures (39-44 degrees C) until Tc reached 39.5 degrees C. Dehydration was produced by 68-72 h of fluid deprivation, which caused increases in plasma osmolality [291 +/- 1 (SE) to 338 +/- 6 mosmol/kg H2O] and sodium concentration (143 +/- 2 to 163 +/- 3 meq/l) and a 16% fall in plasma volume. The primary influence of dehydration was attenuation of the progressive rise in MIBF and iliac conductance (IC) during EH. Absolute MIBF and IC levels at Tc = 39.5 degrees C during EH were 44 and 52%, respectively, lower in the dehydrated state. Also, the MIBF-Tc and IC-Tc linear regression coefficients during EH were lower by 33 and 43%, respectively, in the dehydrated state. Since limb skeletal muscle blood flow does not increase during EH, we conclude that dehydration attenuates the heat stress-induced rise in skin blood flow in baboons, an influence that is similar to what occurs in humans.

Mechanisms producing tachycardia in conscious baboons during environmental heat stress.

The involvement of changes in sympathetic activity, changes in cardiac efferent vagal activity, and nonautonomic mechanisms in producing the rise in heart rate (HR) during heat stress-induced hyperthermia was studied in seven unanesthetized, chronically instrumented baboons (Papio anubis and P. cynocephalus). The experimental protocol consisted of subjecting the baboon to environmental heating (EH) of sufficient intensity (40-45 degrees C) to raise arterial blood temperature (Tbl) 2-3 degrees C in 1-2 h while in one of four states: 1) normal (control), 2) beta-adrenergic receptor blockade induced by propranolol, 3) cholinergic receptor blockade induced by atropine, and 4) combined beta- and cholinergic receptor blockade induced by propranolol and atropine together. HR rose linearly with Tbl during EH in all four states (correlation coefficient greater than or equal to 0.97 in all cases) with average HR-Tbl regression coefficients (slopes) being 20.5 +/- 1.2 (SE) beats X min-1 . degrees C for the normal state, 12.2 +/- 0.5 beats X min-1 . degrees C-1 for the beta-blockade state, 13.3 +/- 1.1 beats X min-1 . degrees C for the cholinergic blockade state, and 8.4 +/- 0.8 beats X min-1 . degrees C-1 for the combined beta- and cholinergic receptor blockade state. Thus nonautonomic mechanisms account for about 40% of the tachycardia in heat-stressed baboons with the remaining 60% produced by combined vagal withdrawal and sympathetic activation. Furthermore application of a multiplicative model of autonomic control of HR to these data suggests that about 75% of the autonomic component is produced by vagal withdrawal.

Influence of heat stress on arterial baroreflex control of heart rate in the baboon.

The influence of environmental heat stress on the arterial baroreflex control of heart rate (HR) was studied in eight conscious, chronically instrumented baboons. Inflations of balloon occluders around the inferior vena cava (IVC) and thoracic descending aorta (DA) were used to produce acute, graded changes in mean arterial blood pressure (MABP) in 5 mm Hg intervals ranging from +/- 5 to +/- 25 mm Hg. After determination of the HR responses to changes in MABP in the normothermic baboon (blood temperature less than or equal to 37.6 degrees C), the animal was subjected to environmental heating to produce hyperthermia. When blood temperature reached approximately 39.5 degrees C, HR responses to graded DA and IVC occlusions were again determined. During hyperthermia, the HR sensitivity (delta HR/ delta MABP) to MABP changes was markedly diminished for reductions in MABP and significantly enhanced for increases in MABP. To determine whether these alterations in the HR response to changes in MABP were due to an alteration of the baroreflex control of HR, full, sigmoid-shaped HR-MABP curves for both the normothermic and hyperthermic states were constructed and characterized by total HR range, estimated slope of the steep portion of the curve, and MABP at the midpoint of the HR range (BP50). During hyperthermia (1) the whole HR-MABP curve shifted significantly upward by 35-40 beats/min, (2) total HR range, the estimated slope, and BP50 did not change, and (3) the control point (pre-occlusion HR-MABP value) curves were also constructed during either beta-adrenergic blockade or cholinergic (Ch)-receptor blockade in the normothermic and hyperthermic state. Similar to that seen for the unblocked heart, the whole HR-MABP curves were also shifted upward during hyperthermia in this group of baboons with no alteration in the total HR range, the estimated slope, or BP50. The upward shift in the HR-MABP curve during Ch-receptor blockade, unlike during beta-receptor blockade, was much greater than that which could be attributed only to the local effect of blood temperature. Although the control point was also shifted upward along the steep portion of the curve during beta- or Ch-receptor blockade, the upward shift observed during beta-adrenergic blockade was similar to that observed in the unblocked state. Thus, a heat stress-induced hyperthermia produces a rise in HR without significantly altering the characteristics of the reflex control of HR by arterial baroreceptors. To rely solely on changes in HR sensitivity may lead to erroneous conclusions as to the effect of a particular stress on the baroreceptor reflex control of HR. Further, these results indicate that: (1) the upward shift in the HR-MABP curve is mediated by both the local effect of blood temperature on HR and cardiac sympathetic efferent neurons which are independent of the baroreceptor reflex, and (2) the upward shift in the control point is mediated predominantly by vagal withdrawal, probably as part of the compensatory response to a heat-induced hypotension.

Influence of skin temperature on central thermoregulatory control of leg blood flow.

This study examined the influence of elevated skin temperature (Tsk) on the central thermoregulatory control of leg blood flow in five unanesthetized, chronically instrumented, resting baboons (Papio anubis and P. cynocephalus). In each experiment, mean iliac blood flow (MIBF), mean arterial blood pressure, arterial blood temperature (Tbl), and Tsk were measured, and iliac vascular conductance (IVC) was calculated. A heat exchanger was incorporated into a chronic arteriovenous femoral shunt to control Tbl. The protocol consisted of raising Tbl approximately 2.6 degrees C in thermoneutral environment (cool Tsk) an then again after Tsk had been elevated by environmental heating. A major influence of raising Tsk was the lowering of threshold Tbl at which the rise in MIBF and IVC commenced. This threshold Tbl was lowered at least 0.8 degrees C on the average. Also, over the whole range of Tbl studied (37.0-39.6 degrees C), MIBF and IVC were higher at high Tsk than at cool Tsk. Thus an elevation of Tsk significantly influences the control of skin blood flow by central thermoreceptors.

alpha-Adrenergic control of intestinal circulation in heat-stressed baboons.

The mechanisms involved in producing intestinal vasoconstriction during a hyperthermia-producing intestinal vasoconstriction during a hyperthermia-producing environmental heat stress are unknown. Five conscious baboons (Papio anubis), each with chronically implanted catheters and a flow probe around the superior mesenteric artery, were subjected to environmental heating (Ta 40-45 degrees C) to raise their arterial blood temperature (Tbl) 2.0-2.6 degrees C to approximately 39.5 degrees C. Accompanying the gradual rise in Tbl was a fall in mean superior mesenteric artery blood flow (MSMF) and a progressive rise in superior mesenteric vascular resistance (SMR). At peak Tbl, MSMF had fallen 28.8 +/- 0.6% (mean +/- SE) and SMR had risen 50.2 +/- 4.2%. To determine the involvement of the sympathetic nervous system in producing this intestinal vasoconstriction, the baboon was subjected to environmental heating after induction of alpha-adrenergic receptor blockade by phenoxybenzamine or phentolamine. In this state, the rise in Tbl was accompanied by no change in MSMF and a slight, but not statistically significant, rise (7.8 +/- 3.8%) in SMR. Since alpha-receptor blockade nearly completely abolishes intestinal vasoconstriction during heat stress, this intestinal vasoconstriction must be mediated primarily by elevated sympathetic outflow.

Control of baboon limb blood flow and heart rate-role of skin vs. core temperature.

To discover the relative importance of body core temperature versus bodyskin temperature in raising limb blood flow and heart rate, we exposed seven unanesthetized, chaired baboons (Papio anubis) to a variety of heating protocols. First, the baboons were exposed to a 40-45 degrees C environment for 0.75-1.5 h. Arterial or right atrial blood temperature (Tbl), skin temperature (Tsk), mean right iliac blood flow (MRIF), and heart rate (HR) all increased gradually during heating. On the average, HR increased from 106 to 160 beats/min and MRIF rose to 286% of control level. To separate influences of Tbl and Tsk on cardiovascular changes, we manipulated Tbl and Tsk independently via a heat exchanger incorporated into a chronic femoral arteriovenous shunt. In most baboons, the MRIF and HR response to a hot environment could be essentially duplicated by elevation of bTbl with Tsk held neutral, while elevation of Tsk with Tbl held neutral had little effect. One baboon exhibited significant response to Tsk elevation with Tbl held neutral, although subsequent manipulation of Tbl overrode this response. We conclude that the normal response to heating in baboons is mainly attributable to drives from internal temperature-sensitive mechanisms. Elevated Tsk shows large effects only in exceptional cases.