Hyperosmolality dilates rat skeletal muscle arterioles: role of endothelial K(ATP) channels and daily exercise.

The purpose of this study was to investigate the mechanism underlying arteriolar responses to hyperosmolality and to determine the effects of daily exercise on this response. Dilator responses were measured in isolated, cannulated, and pressurized skeletal muscle arterioles. Osmolality was increased from approximately 290 to 330 mosmol/kgH(2)O by adding glucose, sucrose, or mannitol to the superfusion solution. All three compounds elicited similar changes in vessel diameter, suggesting that this response was due to changes in osmolality. Responses to glucose were abolished by endothelium removal but were not altered in endothelium-intact vessels by superfusion with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine or the cyclooxygenase inhibitor indomethacin. In endothelium-intact arterioles, responses to glucose superfusion with the ATP-sensitive potassium (K(ATP)) channel inhibitor glibenclamide; however, intraluminal perfusion with glibenclamide nearly abolished the responses to glucose and mannitol. Intraluminal administration of glucose elicited a significantly greater dilation than extraluminal glucose. The response to intraluminal glucose was also inhibited by intraluminal glibenclamide. Four weeks of daily exercise did not significantly alter the responses to hyperosmolality in gracilis or soleus muscle arterioles. These data demonstrate that physiological increases in intraluminal osmolality dilate rat skeletal muscle arterioles via activation of endothelial K(ATP) channels; however, this endothelium-dependent response is not augmented by daily exercise.

Vascular reactivity and baroreflex function during hyperthermia in conscious rats.

The hemodynamic responses to vasoconstrictor agents are blunted during heating in anesthetized rats. It is unknown whether reflex neural responses to these agents are also altered during hyperthermia. Therefore, the purpose of this study was to determine the effect of hyperthermia on the hemodynamic and baroreflex-mediated sympathetic neural responses to vasoactive agents in conscious, unrestrained rats. The splanchnic sympathetic nerve activity (SpNA) and systemic and regional hemodynamic responses to injections of phenylephrine and sodium nitroprusside were measured during normothermia (37 degrees C) and hyperthermia (41.5 degrees C). The hemodynamic responses to phenylephrine and sodium nitroprusside were blunted with heating, whereas the SpNA responses to both agents were augmented or unchanged. At 41.5 degrees C, the baroreflex curves relating heart rate (HR) and SpNA to mean arterial blood pressure were shifted to the right. The operating range and gain of the blood pressure (BP)-HR reflex were significantly reduced during heating, whereas the operating range of the BP-SpNA reflex was augmented at 41.5 degrees C. These results indicate that heating alters the cardiovascular and sympathetic neural responses to vasoactive agents in vivo. Furthermore, the data suggest that heating differentially affects arterial baroreflex control of HR and SpNA, shifting both curves toward higher BP values but selectively attenuating baroreflex control of HR.

Modulation of temperature-induced tone by vasoconstrictor agents.

One of the primary cardiovascular adjustments to hyperthermia is a sympathetically mediated increase in vascular resistance in the viscera. Nonneural factors such as a change in vascular tone or reactivity may also contribute to this response. Therefore, the aim of this study was to determine whether vascular smooth muscle tone is altered during heating to physiologically relevant temperatures >37 degrees C. Gradually increasing bath temperature from 37 degrees C (normothermia) to 43 degrees C (severe hyperthermia) produced graded contractions in vascular ring segments from rat mesenteric arteries and thoracic aortae. In untreated rings these contractions were relatively small, whereas hyperthermia elicited near-maximal increases in tension when rings were constricted with phenylephrine or KCl before heating. In phenylephrine-treated mesenteric arterial rings, the contractile responses to heating were markedly attenuated by the Ca2+ channel antagonists nifedipine and diltiazem. Diltiazem also blocked the contractile responses to heating in thoracic aortic rings. These results demonstrate that hyperthermia has a limited effect on tension generation in rat vascular smooth muscle in the absence of vascular tone. However, in the presence of agonist-induced tone, tension generation during heating is markedly enhanced and dependent on extracellular Ca2+. In conclusion, these data suggest that local regulation of vascular tone can contribute to the hemodynamic adjustments to hyperthermia.

Effect of heating on the hemodynamic responses to vasoactive agents.

During hyperthermia, vasoconstrictor tone in the viscera is lost despite high levels of sympathetic neural outflow and plasma catecholamines, suggesting that vascular responsiveness to adrenergic receptor stimulation is reduced. The purpose of this study was to determine whether adrenoceptor-mediated control of vascular resistance is altered at high body core temperatures. The hemodynamic responses to adrenoceptor agonists were examined in chloralose-anesthetized rats heated to colonic temperatures (Tco) of 37, 39, and 41.5 degrees C. Elevating Tco to 39 degrees C did not alter the hemodynamic responses to any of these agents. Further heating to 41.5 degrees C markedly attenuated the hemodynamic responses to alpha- and beta-adrenoceptor agonists. Similarly, the regional and systemic hemodynamic responses to ANG II and endothelin were also reduced at 41.5 degrees C. In contrast, the hemodynamic responses to endothelium-dependent and -independent vasodilator agents were unchanged or slightly reduced at 41.5 degrees C. The blunted hemodynamic responses observed at 41.5 degrees C indicate that vascular reactivity to vasoconstrictor agents is reduced with hyperthermia and suggest that this nonspecific change in vascular responsiveness may contribute the circulatory collapse associated with high body temperatures.

Effect of heating on vascular reactivity in rat mesenteric arteries.

Vasoconstriction in the viscera is one of the primary cardiovascular adjustments to heating. Local temperature can influence vascular responsiveness to catecholamines and sympathetic nerve activity. Therefore, we hypothesized that heating would alter vascular reactivity in rat mesenteric arteries. Concentration-response curves to norepinephrine, phenylephrine, potassium chloride (KCl), calcium, acetylcholine, and sodium nitroprusside were obtained in vascular ring segments from rat mesenteric arteries at 37 and 41 degrees C. In some rings, basal tension increased slightly during heating. Heating to 41 degrees C did not alter the contractile responses to norepinephrine in endothelium-intact or -denuded rings but augmented the responses to KCl and calcium in endothelium-intact rings. The potentiating effect of heating on the responses to KCl and calcium was eliminated after endothelium removal. In contrast, the relaxant responses to acetylcholine and sodium nitroprusside were significantly attenuated at 41 degrees C. Collectively, these results demonstrate that heating alters vascular reactivity in rat mesenteric arteries. Furthermore, these data imply that heating reduces the ability of vascular smooth muscle to relax, possibly due to a decrease in sensitivity to nitric oxide.

Role of nitrosyl factors in the hemodynamic adjustments to heat stress in the rat.

The present study examined the mechanisms responsible for the hindlimb vasodilation produced by elevating core body (colonic) temperature (Tco) of alpha-chloralose-anesthetized rats from 37 to 39 degrees C. Elevating Tco to 39 degrees C produced equivalent decreases in hindlimb vascular resistance in sham-operated (-48 +/- 2%) and sinoaortic baroreceptor-denervated rats (-44 +/- 3%) rats. There were no changes in mean arterial blood pressure, heart rate, or lumbar sympathetic nerve activity in either group. The prior administration of the alpha 1-adrenoceptor antagonist prazosin (100 micrograms/kg i.v.) did not prevent the heat-induced decrease in hindlimb resistance in sham-operated rats (-52 +/- 7% vs. baseline). In contrast, the fall in hindlimb resistance was markedly attenuated (-20 +/- 5% vs. baseline) in sham-operated rats that had received a prior injection of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (100 mumol/kg i.v.). Dexamethasone (1 mg/kg i.v.), administered to prevent the possible induction of inducible NOS, did not modify the heat-induced hindlimb vasodilation in sham-operated rats (-41 +/- 5%). These results demonstrate that the elevation of Tco to 39 degrees C in alpha-chloralose-anesthetized rats produces a relative vasodilation in the hindlimb that is not obviously linked to an alteration in lumbar sympathetic nerve activity. Because the vasodilation occurred in the presence of prazosin, it is unlikely that the decline in resistance is due to the loss of the vasoconstrictor potency of neurally derived catecholamines. The findings that NG-nitro-L-arginine methyl ester, but not dexamethasone, diminished the heat-induced hindlimb vasodilation suggests that the fall in resistance is due in part to constitutive NOS and supports a role for NOS as a mediator of thermoregulatory active vasodilation.

Modulation of baroreflex sensitivity and spectral power of blood pressure by heat stress and aging.

To investigate the effects of hyperthermia and aging on baroreceptor-heart rate reflex sensitivity (BRS), cardiovascular parameters were recorded during a progressive rise in core temperature in conscious mature and senescent Fischer 344 rats. BRS was calculated from spontaneous changes in blood pressure and interbeat interval. Low- (LF, 0.01-0.20 Hz) and mid- (MF, 0.2-0.5 Hz) frequency blood pressure power were also determined. In both age groups, hyperthermia caused an increase in blood pressure, renal resistance, and LF but no changes in renal nerve activity, whereas a tachycardia was only observed in the older rats. Increases in BRS (0.80 +/- 0.14 vs. 1.72 +/- 0.34 ms/mmHg, P < 0.05) and MF (3.10 +/- 0.55 vs. 7.81 +/- 1.89 mmHg2, P < 0.05) and a positive correlation between BRS and MF (r = 0.50, P < 0.01) were observed with heating in mature but not senescent rats. These results indicate that LF, which increased with elevated core temperature, may be modulated by thermal stimuli. The augmented BRS in the mature group may contribute to the hemodynamic adjustments that occur with hyperthermia, whereas the lack of an increase in BRS during heat stress in the senescent group suggests that baroreceptor reflex modulation is impaired with aging. The positive correlation between BRS and MF in mature rats, together with the lack of an increase in renal sympathetic nerve activity, indicates that MF may reflect the modulating influence of the efferent sympathetic portion of the baroreceptor reflex loop on arterial blood pressure rather than merely the activity of the peripheral sympathetic nervous system.

Aging is not accompanied by sympathetic hyperresponsiveness to air-jet stress.

It has been postulated that sympathetic nervous system reactivity to acutely applied stress is increased with age. We investigated the autonomic and hemodynamic adjustments to air-jet stress in 9 mature (12-mo-old) and 11 senescent (24-mo-old) Fischer 344 rats. Rats were instrumented with arterial and venous catheters, flow probes around the renal artery, and nerve electrodes on the ipsilateral renal nerve. After the rats recovered from surgery, blood pressure, heart rate, renal blood flow, and renal sympathetic nerve activity were recorded during control conditions and during an 8-min continuous air-jet application. Renal resistance and the low (0.01-0.20 Hz)- and mid-frequency (0.20-0.50 Hz) power of blood pressure were computed off-line. The air jet induced an increase in blood pressure, heart rate, renal resistance, renal nerve activity, and blood pressure power in the low- and mid-frequency ranges in both groups. Blood pressure and low-frequency blood pressure power increased less, and the elevations in renal resistance and renal nerve activity were of shorter duration in senescent compared with mature rats. These data suggest that sympathetic responsiveness to air-jet stress is not enhanced with increasing age.

Cardiovascular and sympathoadrenal responses to heat stress following water deprivation in rats.

This study was designed to characterize the regional and systemic hemodynamic and sympathoadrenal responses to heating after 24 and 48 h of water deprivation in chloralose-anesthetized, male Sprague-Dawley rats (n = 7 per group). Water deprivation produced significant decreases in body weight of 8.1 and 13.7% in the 24- and 48-h groups (P < 0.05), respectively. After water deprivation, rats were exposed to an ambient temperature of 43 degrees C. After correction for body weight differences, heating rates were faster in the 48-h group compared with both euhydrated and 24-h groups. Mean arterial blood pressure (MAP), heart rate, and colonic (Tco) and tail (Ttail) temperatures increased above baseline in all groups during heating. Renal and mesenteric artery blood flow velocities decreased, and vascular resistances increased in response to heating. Compared with euhydrated controls, 48-h water-deprived rats exhibited attenuated pressor (delta MAP = 36 +/- 3 vs. 18 +/- 3 mmHg) and visceral vasoconstrictor (% delta in mesenteric resistance = 122.6 +/- 27.3 vs. 54.9 +/- 6.9%) responses during heating. Tail-skin blood flow estimated from Ttail was also lower at baseline and the onset of heating in water-deprived rats. However, peak Ttail and Tco values were similar across groups. Plasma catecholamines measured in separate groups of rats (n = 6 per group) were significantly higher at baseline and the end of heating in the 48-h group compared with euhydrated and 24-h groups. Despite this exaggerated sympathoadrenal response, the 48-h group exhibited attenuated hemodynamic responses to nonexertional heating compared with euhydrated and 24-h water-deprived rats. These data suggest that cardiovascular and thermoregulatory adjustments can compensate for small changes in hydration state (i.e., 24 h), but more severe levels of hypohydration significantly alter blood pressure and body temperature regulation during heat stress.

Detection of small changes in body composition by dual-energy x-ray absorptiometry.

The ability of dual-energy x-ray absorptiometry (DEXA) to detect small changes in body composition was studied in 17 men and women during a dehydration-rehydration protocol. Scale weight (BW) and total mass (TM) from DEXA were highly related (r > 0.99) as were estimates of fat-free mass (r = 0.99) and percent fat (r = 0.97) from DEXA and densitometry. Changes in BW of approximately 1.5 kg due to fluid loss and gain were highly correlated (r = 0.90) with both changes in TM and soft-tissue mass (STM) by DEXA but less so (r = 0.67) with changes in lean-tissue mass (LTM). Mean changes in TM, STM, and LTM were not different (P > 0.05) from changes in BW. Estimates of bone mass and fat were unaffected by changes in hydration. We conclude that DEXA is able to detect small individual changes in TM and STM and is also useful for detecting group changes in LTM.