Central baroreflex resetting as a means of increasing and decreasing sympathetic outflow and arterial pressure.

The arterial baroreflex has two important functions. First, the arterial baroreflex is a negative feedback reflex that regulates arterial pressure around a preset value called a set or operating point. Second, the arterial baroreflex also establishes the prevailing systemic arterial pressure when the operating point is reset. That is, modulating the response of barosensitive neurons in the central nervous system (CNS) establishes the operating point or prevailing systemic arterial pressure. Therefore, the operating point of the arterial baroreflex is not fixed, but is variable over a wide range of pressures and is determined by a variety of inputs from the peripheral and central nervous systems. At the onset of dynamic exercise, heart rate (HR) and sympathetic nerve activity (SNA) increase abruptly and dramatically. The initial increase in HR and SNA is mediated by central command. Central command operates by resetting the operating point of the arterial baroreflex to a higher pressure. In this situation, the operating point of the arterial baroreflex is above the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by activating SNA and inhibiting parasympathetic nerve activity, which increases cardiac output and peripheral resistance and, consequently, arterial pressure. After exercise, loss of central command and enhanced activity of the cardiopulmonary reflex resets the operating point of the arterial baroreflex to a lower pressure. In this situation, the operating point of the arterial baroreflex is below the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by inhibiting SNA, which decreases peripheral resistance and consequently arterial pressure. In these situations, central resetting of the arterial baroreflex is a means of increasing and decreasing sympathetic outflow and arterial pressure.

Angiotensin II acutely attenuates range of arterial baroreflex control of renal sympathetic nerve activity.

Acutely increasing peripheral angiotensin II (ANG II) reduces the maximum renal sympathetic nerve activity (RSNA) observed at low mean arterial blood pressures (MAPs). We postulated that this observation could be explained by the action of ANG II to acutely increase arterial blood pressure or increase circulating arginine vasopressin (AVP). Sustained increases in MAP and increases in circulating AVP have previously been shown to attenuate maximum RSNA at low MAP. In conscious rabbits pretreated with an AVP V1 receptor antagonist, we compared the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng x kg(-1) x min(-1)) on the relationship between MAP and RSNA when the acute pressor action of ANG II was left unopposed with that when the acute pressor action of ANG II was opposed by a simultaneous infusion of sodium nitroprusside (SNP). Intravenous infusion of ANG II resulted in a dose-related attenuation of the maximum RSNA observed at low MAP. When the acute pressor action of ANG II was prevented by SNP, maximum RSNA at low MAP was attenuated, similar to that observed when ANG II acutely increased MAP. In contrast, intravertebral infusion of ANG II attenuated maximum RSNA at low MAP significantly more than when administered intravenously. The results of this study suggest that ANG II may act within the central nervous system to acutely attenuate the maximum RSNA observed at low MAP.

Angiotensin II modulation of the arterial baroreflex: role of the area postrema.

1. Resetting the operating point of the arterial baroreflex appears to be an important factor involved in determining the level of sympathetic outflow. 2. Substantial data indicate that circulating angiotensin (Ang)II can reset the arterial baroreflex to higher operating pressures. 3. This action of AngII to increase the level of sympathetic nervous system outflow relative to blood pressure may contribute to elevated mean arterial pressure (MAP) during AngII hypertension, as well as to the maintenance of MAP during low sodium states. 4. In most instances, the resetting observed during elevated peripheral AngII is dependent on the area postrema (AP). 5. Although the central mechanisms by which the arterial baroreflex resets to different operating pressures remain to be completely defined, the AP may provide a separate mechanism whereby humoral factors can modulate the operating point of the arterial baroreflex.

ANG II and baroreflex function in rabbits with CHF and lesions of the area postrema.

Blockade of the angiotensin II (ANG II) type 1 receptor (AT(1)) has been shown to restore baroreflex sensitivity in rats and rabbits with experimental chronic heart failure (CHF). Because the modulation of baroreflex function in response to ANG II is mediated in part by AT(1) receptors located in the area postrema, we hypothesized that lesions of the area postrema would prevent the enhancement in baroreflex function in response to AT(1)-receptor blockade in rabbits with pacing-induced CHF. Experiments were carried out on 24 male New Zealand White rabbits that were divided into sham (n = 12) and lesioned (n = 12) groups further divided into normal and CHF subgroups (n = 6 each). All rabbits were identically instrumented to measure cardiac external dimensions, central venous pressure, arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA). After 3-4 wk of pacing, baroreflex sensitivity (infusions of phenylephrine and nitroprusside) was evaluated before and after intravenous administration of the AT(1)-receptor antagonist L-158,809. Maximum baroreflex sensitivity in nonpaced rabbits was 5.4 +/- 0.7 beats. min(-1). mmHg(-1) and 5.2 +/- 0.5% of maximum/mmHg for HR and RSNA curves, respectively, and was not altered by L-158,809 in either intact or lesioned rabbits. In contrast, L-158,809 enhanced baroreflex sensitivity in intact rabbits with CHF (HR from 1.6 +/- 0.3 to 4.1 +/- 0.7 beats. min(-1). mmHg(-1), P < 0.001; RSNA from 2.3 +/- 0.2 to 4.9 +/- 0.4% of maximum/mmHg, P < 0.001). However, in CHF rabbits with area postrema lesions, L-158,809 failed to enhance baroreflex sensitivity. Interestingly, area postrema lesions did not normalize the baroreflex in CHF rabbits. From these data we conclude that the area postrema mediates the normalization of baroreflex sensitivity after AT(1) blockade in rabbits with CHF but does not modify resting baroreflex function.

Suppression of renal sympathetic nerve activity during portal vein infusion of hypertonic saline.

Sodium ions absorbed from the intestine are postulated to act on the liver to reflexly suppress renal sympathetic nerve activity (RSNA), resulting in inhibition of sodium reabsorption in the kidney. To test the hypothesis that the renal sympathoinhibitory response to portal venous NaCl infusion involves an action of arginine vasopressin (AVP) at the area postrema, we examined the effects of portal venous infusion of hypertonic NaCl on RSNA before and after lesioning of the area postrema (APL) or after pretreatment with an AVP V1 receptor antagonist (AVPX). Rabbits were chronically instrumented with portal and femoral venous catheters, femoral arterial catheters, and renal nerve electrodes. Portal venous infusion of 9.0% NaCl (0.02, 0.05, 0.10, and 0.15 ml.kg-1.min-1 of 9.0% NaCl for 10 min) produced a dose-dependent suppression of RSNA (-12 +/- 3, -34 +/- 3, -62 +/- 5, and 80 +/- 2%, respectively) that was greater than that produced by femoral vein infusion of 9.0% NaCl (2 +/- 3, -3 +/- 2, -12 +/- 4, and -33 +/- 3%, respectively). The suppression of RSNA produced by portal vein infusion of 9.0% NaCl was partially reversed by pretreatment with AVPX (-9 +/- 3, -20 +/- 3, -41 +/- 4, and -55 +/- 4%, respectively) and by APL (-11 +/- 2, -25 +/- 2, -49 +/- 3, and -59 +/- 6%, respectively). There were no significant differences between the effects of AVPX and APL, and the effect of APL was not augmented by AVPX. These results indicate that the suppression of RSNA due to portal venous infusion of 9.0% NaCl involves an action of AVP via the area postrema.

Long-term effects of AVP-induced neurohumoral interaction via area postrema on body fluid and blood pressure.

Arginine vasopressin (AVP) has been known to interact with the central nervous system via the area postrema (AP), resulting in suppression of renal sympathetic outflow in short-term studies. We hypothesize that if this sympathoinhibitory effect lasts long, then the neurohumoral interaction would enhance urinary output because of the suppression of neurogenic reuptake of sodium (Na+) and water. Intact (Int) and AP-lesioned (APX) rabbits were chronically catheterized and housed in metabolic cages. AVP was intravenously infused (0.1 mU.kg-1.min-1) for 5 consecutive days. Urine volume and urinary Na+ excretion rates in Int rabbits were lower than those in APX rabbits during AVP infusion. This smaller urinary output in Int rabbits was reconfirmed either from the daily balance of water and Na+ or from the body weight, plasma Na+ concentration, and plasma osmolality data. This result contradicted the hypothesis. Mean arterial pressure was not altered in either group of rabbits while heart rate was suppressed in the Int rabbits. These data suggest that AP-mediated long-term action of AVP augments water retention and sustains bradycardia.

Daily exercise attenuates the sympathetic nerve response to exercise by enhancing cardiac afferents.

"Central command" may initiate the sympathoexcitatory responses at the onset of exercise by shifting the operating point of the arterial baroreflex toward higher pressures. Daily exercise (DE) attenuates the sympathoexcitatory responses to submaximal exercise. This DE-induced adaptation may be due, in part, to an enhanced inhibitory influence of cardiac afferents. This is suggested because cardiac afferents exert a tonic inhibitory influence on the arterial baroreflex which is enhanced by DE. Therefore, the influence of cardiac afferents on the regulation of renal sympathetic nerve activity (RSNA) during exercise was examined in a group of sedentary and age-matched DE rabbits. The rabbits were instrumented with a Silastic catheter inserted into the pericardial sac, electrodes around the renal sympathetic nerves, and catheters in the femoral artery and vein. In the sedentary rabbits, treadmill exercise (12 m/min, 20% grade) significantly increased mean arterial pressure (delta 18 +/- 3 mmHg), heart rate (delta 36 +/- 3 beats/min), and RSNA (delta 295 +/- 23%). More importantly, cardiac afferent blockade (2% intrapericardial procainamide) did not significantly alter the RSNA response to exercise in the sedentary rabbits. DE did not alter the mean arterial pressure (delta 15 +/- 1 mmHg) or heart rate (delta 55 +/- 8 beats/min) response to exercise; however, RSNA (delta 252 +/- 9%) was significantly reduced. In contrast to the sedentary rabbits, cardiac afferent blockade in the DE rabbits significantly increased the RSNA response to exercise (delta 417 +/- 30%). These results suggest that DE attenuates the RSNA response to dynamic exercise due, in part, to an enhanced inhibitory influence of cardiac afferents.

The roles of cGMP and cAMP in active thermoregulatory vasodilation.

This study was designed to test the hypothesis that active thermoregulatory vasodilation (AVD) is the result of a neurotransmitter-induced adenosine 3',5'-cyclic monophosphate (cAMP) pathway interacting with a nitric oxide-induced guanosine 3',5'-cyclic monophosphate (cGMP) pathway. Rabbits were instrumented for measurement of arterial pressure and ear blood flow (EBF) and the infusion of drugs. In four groups of conscious animals, whole-body heating increased EBF from 0.5 +/- 0.3 to 8.3 +/- 1.3 kHz. In group 1 (n = 6), N(omega)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 10-40 mg) reduced EBF from 7.1 +/- 0.9 to 1.9 +/- 0.5 kHz. Subsequent infusion of 8-bromo-cGMP (a cGMP analog, 5-10 mg) returned EBF to 6.2 +/- 0.7 kHz. In group 2 (n = 3), (R)-p-adenosine 3',5'-cyclic monophosphothioate (a cAMP-dependent protein kinase inhibitor, 10 mg) reduced EBF to 1.6 +/- 0.4 kHz. In group 3 (n = 6), nerve blockade of the ear (procaine, 20 mg/ml, 1.5 ml) reduced EBF from 8.6 +/- 1.3 to 1.6 +/- 0.3 kHz. Subsequent infusion of 8-bromo-cAMP (a cAMP analog, 5-10 mg) returned EBF to 8.3 +/- 2.0 kHz. In group 4 (n = 6), the infusion of L-NAME caused EBF to fall from 9.0 +/- 1.1 to 1.2 +/- 0.3 kHz. Infusion of the cAMP phosphodiesterase inhibitor Ro 20-1724 (0.2-0.5 mg) raised EBF to 5.5 +/- 0.7 kHz. These results suggest that cGMP plays a permissive role in AVD and indicate that the transmitter acts through cAMP.

Administration of AVP to the area postrema alters response of NTS neurons to afferent inputs.

This study was designed to determine if arginine vasopressin (AVP) facilitates the response of nucleus of the solitary tract (NTS) neurons to baroreceptor input. In anesthetized sinoaortic-denervated vagotomized rabbits, AVP was intravenously infused (15 microg x kg(-1) x min(-1), 1 min) or microinjected into the area postrema (AP; 1 ng/nl, 10 nl). Extracellular recordings of evoked NTS neuronal responses to electrical stimulation of the aortic depressor nerve (ADN) or vagus nerve (1 Hz, 2-20 V, 0.05-0.6 ms) were evaluated before and after AVP administration. In neurons receiving input from the ADN (n = 19), 58% of them increased their responses after AVP (40.3 +/- 5.0 to 71.5 +/- 4,8%, P < 0.001). Similarly, in neurons activated by vagal stimulation (n = 22), 55% of them were facilitated during AVP administration (59.7 +/- 12.8 to 90.8 +/- 10.7%, P < 0.01). This action of AVP was independent of the mode of AVP administration, since either microinjection or venous infusion was effective in augmenting responses of NTS neurons to aortic/vagal stimulation. In an additional 37 spontaneous NTS neurons, AVP showed no effect on the mean baseline firing rate (8.9 +/- 1.3 vs. 9.6 +/- 1.3 spikes/s, P > 0.05), but increased neuronal activity in 54% of neurons (6.9 +/- 1.3 vs. 13.1 +/- 1.7 spikes/s, P < 0.01). In two rabbits pretreated with vasopressin antagonist (15 microg/kg iv), AVP failed to produce facilitatory effects (n = 8). The results of this study provide evidence in support of the hypothesis that circulating peptides modulate the arterial baroreflex via activation of neurons in the AP.

Sympathoexcitatory response to cyclosporin A and baroreflex resetting.

We postulate that the sympathoexcitatory response associated with the immunosuppressive agent cyclosporin A is due to an upward resetting of the arterial baroreflex. We performed studies in conscious intact and sinoaortic-denervated rabbits instrumented with catheters and renal nerve electrodes. In intact rabbits, cyclosporin A (20 mg/kg i.v., 30 minutes) produced significant increases in renal sympathetic nerve activity (100% to 269 +/- 74%, P < .05) but did not increase mean arterial pressure. In intact rabbits, we determined arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure by producing ramp increases (intravenous phenylephrine) and decreases (intravenous nitroprusside) in mean arterial pressure. Cyclosporin A treatment produced a shift of the midrange of the baroreflex control of heart rate (78.0 +/- 4.1 to 84.6 +/- 4.7 mm Hg, P < .05) and renal sympathetic nerve activity (74.6 +/- 3.9 to 87.0 +/- 4.8 mm Hg, P < .05). Vehicle administration produced no effects on arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure. Compared with vehicle treatment, cyclosporin A reduced the maximum gain of heart rate (-5.6 +/- 0.6 versus -3.1 +/- 0.8 beats per minute per millimeter of mercury, P < .05) but had no effect on the maximum gain of renal sympathetic nerve activity. In conscious sinoaortic-denervated rabbits, cyclosporin A had no effect on mean arterial pressure (95.7 +/- 7.3 to 91.8 +/- 10.8 mm Hg), renal sympathetic nerve activity (100% to 110 +/- 6%). and heart rate (287 +/- 10 to 279 +/- 8 beats per minute). However, when the same sinoaortic-denervated rabbits were anesthetized with sodium pentobarbital, cyclosporin A (20 mg/kg i.v.) produced increases in renal sympathetic nerve activity (100% to 189 +/- 27%). These data indicate (1) that the sympathoexcitatory response to cyclosporin A depends on baroreceptor afferent input in the conscious state and (2) that this response involves an upward resetting of the arterial baroreflex.

Interactions between vasopressin and baroreflex control of the sympathetic nervous system.

1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho-inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho-excitation to a decrease in pressure is reduced. 2. Evidence suggests that vasopressin may influence cardiovascular reflex function at multiple sites. Nevertheless, the primary site involved in the effects of circulating vasopressin on baroreflex function appears to be in the central nervous system, specifically in the area postrema. Lesion of the area postrema abolishes the ability of circulating vasopressin to modulate arterial baroreflex and cardiopulmonary reflex function and electrical or chemical stimulation of this circumventricular organ mimics the effects of vasopressin. In addition, vasopressin has been shown to influence the activity of area postrema neurons in vivo and in vitro. Although not all studies agree, the effects of the area postrema and vasopressin on cardiovascular reflex function appear to be dependent on afferent input from peripheral baroreceptors. 3. Most evidence suggests that vasopressin exerts its effects on baroreflex function through a V1 vasopressin receptor mechanism. Systemic administration or microinjection into the area postrema of a specific V1 receptor antagonist abolishes the action of arginine vasopressin on arterial baroreflex and cardiopulmonary reflex control of the sympathetic nervous system. 4. The ability of vasopressin and the area postrema to influence baroreflex function appears to be dependent on an alpha 2-adrenoceptor mechanism at the level of the nucleus tractus solitarius (NTS). Blockade of alpha 2-adrenoceptors in the NTS abolishes the effects of vasopressin and the area postrema on the sympathetic nervous system. Facilitation of NTS processing of baroreceptor afferent inputs by the area postrema could contribute to the enhanced sympatho-inhibition and shift of the baroreflex curve to lower pressures during elevations in circulating vasopressin.

Arterial baroreflex modulation of heat-induced vasodilation in the rabbit ear.

The purpose of this study was to determine whether nonthermal baroreflexes arising from cardiopulmonary and/or arterial baroreceptors modulate rabbit ear blood flow (EBF) during hyperthermia. Intact and sinoaortic-denervated (SAD) rabbits were chronically instrumented with a Doppler ultrasonic flow probe for measurement of EBF velocity (kHz). During whole body heating in conscious rabbits, EBF and ear vascular conductance (EVC) increased as core temperature increased until maximal plateau levels of EBF and EVC were reached. The maximal plateau level of EVC attained during heat stress was lower in SAD than in intact rabbits. Subsequent intrapericardial administration of procaine at maximal EBF blocked cardiac afferents but did not alter EVC in either animal group. In a second experiment, ramp decreases in mean arterial pressure were produced by vena caval occlusion at maximal EBF. In intact rabbits, EBF and EVC decreased linearly as mean arterial pressure fell, but EBF and EVC did not decrease during vena caval occlusion in SAD rabbits. Thus neither pharmacological nor mechanical unloading of cardiac baroreceptors results in reflex vasoconstriction in the heat-stressed rabbit ear. However, baroreflexes arising from arterial baroreceptors may modulate EBF in heat-stressed rabbits.

Subcellular mechanisms of angiotensin II and arginine vasopressin activation of area postrema neurons.

Angiotensin II (ANG II) and arginine vasopressin (AVP) act on area postrema (AP) neurons to modulate the baroreflex. Because activation of AP neurons by either ANG II or AVP increases intracellular free Ca2+ concentrations ([Ca2+]i), the goal of this study was to analyze the factors affecting the [Ca2+]i responses to ANG II and AVP. Neurons were recovered from 14- to 16-day old rats and studied after 8-14 days in culture by use of the microscopic digital image analysis for fura 2-loaded cells. The effects of ANG II (100 nM) and AVP (100 nM) on [Ca2+]i were determined in normal (2 mM) and low (< 10 nM) extracellular Ca2+ concentrations. In 143 of 240 neurons, ANG II increased [Ca2+]i 4.65-fold after 20 s, and a similar response was observed in the absence of extracellular Ca2+ (3.65-fold after 20 s). After 60 s of observation, steady-state levels of increased [Ca2+]i were still present under both conditions. Pretreatment with AT1 antagonist or pertussis toxin abolished the response to ANG II. AVP also increased [Ca2+]i (3.6-fold at peak, 20 s) in normal and low extracellular Ca2+. Pretreatment with AVP V1 antagonist or pertussis toxin abolished the response to AVP. This study indicates that ANG II-induced increases in [Ca2+]i are independent of extracellular Ca2+ concentrations and involve the activation of AT1 receptors and a pertussis toxin-sensitive G protein. Although AVP affects a fewer number of AP neurons, the mechanisms of activation are also independent of extracellular Ca2+ concentration and are mediated by a pertussis toxin-sensitive G protein.

Synaptic connections and interactions between area postrema and nucleus tractus solitarius.

The purpose of this study was to examine whether there are separate excitatory and inhibitory pathways from the area postrema (AP) to the nucleus tractus solitarius (NTS) and to examine the synaptic interactions between inputs from the AP and solitary tract (ST) on the NTS neurons. The following observations were made: (1) the predominant projections from the AP to the NTS were excitatory. Among the cells that had AP input, 90% of the cells (43/48) were excited by AP stimulation while 10% (5/48) of the cells were inhibited; (2) inputs from the AP and ST mainly summated occlusively on the NTS neurons, but at near threshold of discharge, the input from one source could facilitate the generation of action potentials induced by the other; and (3) single conditioning stimulation of the AP did not significantly inhibit the NTS neuronal response to ST stimulation, but stimulation of the AP with a train of high frequency stimuli inhibited the response of NTS neurons to ST stimulation and inhibited the evoked response to AP stimulation. The results of this study may help in the understanding of the modulatory role of the AP in the baroreflex and the integration process in the NTS.

Effect of vasopressin on baroreflex control of lumbar sympathetic nerve activity and hindquarter resistance.

Arginine vasopressin (AVP) has been shown to increase the inhibitory influence of the baroreflex on sympathetic nerve activity by a mechanism involving receptors located in the area postrema. The purpose of these experiments was to study the functional effect of this action of AVP by testing the hypothesis that AVP can buffer its own vasoconstrictor effect by facilitating baroreflex-mediated withdrawal of sympathetic nerve activity. Specifically, we determined 1) if AVP can attenuate increases in hindquarter vascular resistance during the infusion of another vasoconstrictor, phenylephrine, and 2) whether the effects of AVP on vascular resistance are associated with appropriate corresponding changes in lumbar sympathetic nerve activity (LSNA). In pentobarbital-anesthetized New Zealand White rabbits the baroreflex was stimulated by phenylephrine-induced elevations in arterial pressure. Baroreflex-mediated changes in heart rate (HR), calculated hindquarter vascular resistance index (R), and LSNA were determined during the simultaneous intravertebral infusion of AVP (0, 0.5, or 1.0 ng.kg-1, min-1). Intravertebral infusion of AVP alone had no effect on resting mean arterial pressure (MAP) but reduced baseline values for LSNA and HR. Intravenous infusion of phenylephrine alone produced dose-dependent increases in MAP and R and decreases in LSNA and HR. The simultaneous infusion of AVP (0.5 or 1.0 ng.kg-1 min-1) and phenylephrine (1.25, 2.5, 5.0, 7.5, and 10.0 micrograms.kg-1.min-1) had no effect on the increase in MAP but attenuated the increases in R and facilitated the reductions in LSNA at all doses of phenylephrine. The higher dose of AVP also enhanced the phenylephrine-induced reductions in HR. In contrast, the intravenous infusion of AVP (1.0 ng.kg-1.min-1) did not alter baroreflex-mediated changes in R, LSNA, or HR. Therefore, we conclude that the action of AVP to increase baroreflex-mediated sympathoinhibition results in an attenuated rise in hindquarter vascular resistance during the infusion of another vasoconstrictor, phenylephrine.

Permissive role for nitric oxide in active thermoregulatory vasodilation in rabbit ear.

The present study was designed to test the hypothesis that during whole body heating (WBH), nitric oxide (NO) synthesized in the endothelium acts synergistically with an unknown neurotransmitter to elicit active vasodilation. Rabbits were instrumented for the measurement of mean arterial pressure, heart rate, and ear blood flow (EBF) (Doppler ultrasound). During WBH, either N omega-nitro-L-arginine methyl ester (L-NAME, 10-40 mg over 10-15 min, n = 6 rabbits; group 1), a NO synthase inhibitor, or saponin (30-40 mg over 10-20 min, n = 6 rabbits; group 2), a detergent that denudes the endothelium, was given via a lingual artery catheter until thermoregulatory vasodilation was reversed. When EBF stabilized at the new reduced level, the NO donor, sodium nitroprusside (SNP), was infused (0.2-1.0 mg/ml, 0.01-0.05 ml/min, 2-5 min) via the lingual artery catheter. During WBH, EBF increased from 0.39 +/- 0.08 to 6.47 +/- 0.63 kHz in group 1, and from 0.69 +/- 0.18 to 5.72 +/- 0.49 kHz in group 2. Infusion of L-NAME decreased EBF in group 1 to 1.97 +/- 0.40 kHz. Infusion of saponin decreased EBF in group 2 to 1.23 +/- 0.40 kHz. Subsequent SNP infusion during hyperthermia returned EBF to 6.88 +/- 0.72 kHz in group 1 and 5.53 +/- 1.27 kHz in group 2 but had no effect when administered during normothermia. These results suggest that NO acts in conjunction with another substance, presumably the neurotransmitter released on WBH, to elicit thermoregulatory vasodilation.

Angiotensin II modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism in rabbits.

To test the hypothesis that angiotensin II (ANG II) modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism, we examined the effects of intravertebral infusion of ANG II on baroreflex function curves before and after intravertebral administration of the alpha 1-adrenoreceptor antagonist prazosin. Rabbits were chronically instrumented with subclavian and vertebral arterial catheters, venous catheters, and aortic and vena caval occludes. Baroreflex curves were obtained by relating heart rate (HR) to mean arterial pressure during increases and decreases in arterial pressure. Intravertebral infusions of ANG II (5, 10, and 20 ng.kg-1.min-1) produced a dose-dependent shift of the midrange of the curve toward higher pressures (64 +/- 1 to 68 +/- 1, 76 +/- 1, and 85 +/- 2 mmHg, respectively). Pretreatment with prazosin (10 micrograms/kg) via the vertebral artery markedly reduced the shift in the baroreflex curve induced by the highest dose of ANG II (64 +/- 2 to 70 +/- 2 mmHg). These data suggest that ANG II resets the operating point of the HR baroreflex curve to a higher blood pressure and that this effect is mediated via a central alpha 1 mechanism. When the effects of vertebral ANG II on the baroreflex control of renal sympathetic nerve activity (RSNA) were examined, intravertebral administration of ANG II, while reducing the gain and the maximum RSNA, did not reset the RSNA baroreflex curve. These data suggest that ANG II acutely resets the HR baroreflex but not the RSNA baroreflex and that the resetting involves an alpha 1-adrenergic mechanism.

Effects of arginine vasopressin and angiotensin II on area postrema neurons in rabbit brain slice preparation.

Previous in vivo studies have indicated that both arginine vasopressin (AVP) and angiotensin II (ANG II) can modulate the baroreflex by acting on the area postrema (AP). In the present study, effects of AVP and ANG II on AP neuronal activity were investigated by recording extracellular activity in a rabbit brainstem slice preparation. AVP (1 nM-1 microM) inhibited 14.5% and excited 53.2% of the neurons while ANG II (1 nM-5 microM) inhibited 32.3% and excited 29% of the neurons. Application of AVP and ANG II to the same AP neurons at the same concentration indicated that more AP neurons responded to AVP than to ANG II. ANG II induced more inhibitory responses than AVP. The results suggest that AVP and ANG II may produce different effects on the baroreflex by acting on different pools of AP neurons and by exerting different effects on the same AP neuron.

Pregnancy attenuates activity of the baroreceptor reflex.

1. Pregnancy-induced changes in acute blood pressure regulation are reviewed. 2. Pregnant animals are less able to maintain arterial pressure during haemorrhage than non-pregnant animals. 3. Baroreceptor reflex-mediated increases in heart rate, renal sympathetic activity, vasopressin, ACTH and cortisol are reduced during pregnancy. Therefore, one explanation for the subnormal ability of pregnant animals to regulate arterial pressure during haemorrhage is that the baroreceptor reflex is not as effective. 4. Chronic increases in oestrogen levels in non-pregnant rabbits do not reduce the gain of baroreflex control of renal sympathetic activity. This and other findings suggest that oestrogen alone does not mediate the blunted baroreflex activity observed during pregnancy.

Angiotensin II-dependent hypertension and the arterial baroreflex.

Angiotensin II (ANG II)-dependent hypertension involves the resetting of the heart rate (HR) and sympathetic baroreflex toward higher pressures in conscious rabbits. The resetting of the HR baroreflex function occurs within minutes of the administration of ANG II, while the resetting of the sympathetic baroreflex requires several days. In conscious rabbits, an intact area postrema (AP) is required for the resetting of either the HR or sympathetic baroreflex function. Data is also presented showing that pretreatment with an alpha-1 adrenergic receptor antagonist prevents the early resetting of the HR baroreflex.