Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.     

Effect of hemorrhage on plasma atriopeptin levels in conscious dogs

An increase in atrial pressure has been shown to cause an increase in the concentration of atrial peptides (atriopeptin) in plasma. We therefore hypothesized that a reduction in atrial pressure would decrease the concentration of atriopeptin in plasma. In formulating this hypothesis we assumed that changes in the concentration of other circulating hormones or changes in cardiac nerve activity during hemorrhage would not affect the secretion of atriopeptin. To test the hypothesis, we bled sham-operated conscious dogs at a rate of 0.8 ml.kg-1.min-1 to decrease right and left atrial pressures. Hemorrhage was continued until a total of 30 ml of blood per kilogram body weight had been removed. Identical experiments were performed on conscious cardiac-denervated dogs. The concentration of plasma atriopeptin was decreased in each group of dogs after 10 ml of blood per kilogram of body weight had been removed, but the decrease achieved statistical significance only in the cardiac-denervated dogs. Further hemorrhage, however, produced no further decreases in circulating atriopeptin in either group even though atrial pressures continued to decline as more blood was removed. A comparison of the atriopeptin response to hemorrhage revealed no significant difference between the sham-operated and cardiac-denervated dogs, thus providing no evidence for a specific effect of cardiac nerves on atriopeptin secretion during hemorrhage. Our results demonstrate that the relationship between atrial pressure and plasma atriopeptin that has been observed repeatedly during atrial stretch is not evident during relatively slow, prolonged hemorrhage. There is, however, a small decline in circulating atriopeptin during the initial stage of hemorrhage that could be of biological significance.     

Atriopeptin alters the vasopressin and renin responses elicited by hemorrhage

This study was designed to investigate whether an infusion of atrial peptide is capable of modulating the hormonal and hemodynamic responses elicited by acute hemorrhage. Conscious dogs were bled at a rate of 0.8 ml.kg-1.min-1 until 20 ml of blood/kg body wt had been removed. Two experiments were performed on each dog; in one experiment the animal was given alpha-human atrial natriuretic peptide (alpha-hANP) (50 ng.kg-1.min-1) dissolved in saline; in the other only the saline vehicle was given. Right and left atrial pressures decreased during hemorrhage in all experiments; the absolute decreases were greater when the animals received atriopeptin, but the differences between treatments were statistically significant only for right atrial pressure. Cardiac output decreased (P less than 0.05) and total peripheral resistance increased (P less than 0.05) during hemorrhage when atriopeptin was infused; although these variables showed similar trends when vehicle alone was infused during hemorrhage, no significant changes occurred. Infusion of atrial peptide did not affect the decrease in arterial blood pressure that occurred during hemorrhage. The increase in plasma vasopressin induced by hemorrhage was potentiated, but the increase in plasma renin activity was attenuated when alpha-hANP was infused. Hemorrhage increased circulating aldosterone levels in each experiment, but the response was less pronounced when alpha-hANP was given during the experiment. Intravenous administration of alpha-hANP modulates the hemodynamic responses elicited by hemorrhage, potentiates the rise in plasma vasopressin, and attenuates the rise in plasma renin activity induced by acute blood loss in conscious dogs.     

Cardiovascular and renin responses to vanadate in the conscious dog: attenuation after calcium channel blockade

The effects of vanadate on cardiovascular function and on the secretion of renin and vasopressin were investigated by infusing sodium orthovanadate (0.32 mu mole/kg X min) intravenously into five conscious dogs. Vanadate caused significant increases in mean arterial pressure, total peripheral resistance, pulmonary arterial pressure, and cardiac output. These data illustrate that the hemodynamic effects of vanadate in the conscious dog are similar to those of the anesthetized dog but that minor differences do exist. Vanadate significantly suppressed plasma renin activity, but plasma vasopressin was unchanged. The effects of vanadate also were investigated in the same dogs on another day after administration of the calcium channel blocker, verapamil (0.3 mg/kg bolus + 0.01 mg/kg X min). After calcium channel blockade, the increases in arterial pressure and pulmonary arterial pressure induced by vanadate were attenuated, and cardiac output did not increase. Calcium channel blockade also prevented the vanadate-induced decrease in plasma renin activity. These data suggest that the cardiovascular and humoral alterations produced by vanadate in the conscious dog are at least partially mediated by changes in intracellular calcium.     

Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena caval constriction in dogs

We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs (n = 8). The mean coefficient of determination (r(2)) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a significant difference between the means (P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002, respectively, and the means were not significantly different (P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.     

Systemic and renal hemodynamic responses to vascular blockade of vasopressin in conscious dogs with ascites

A role for arginine vasopressin has been implicated in the compensatory control of arterial blood pressure in several animal models with reported increases in plasma levels of arginine vasopressin. A threefold elevation in plasma vasopressin has been reported in conscious dogs following constriction of the inferior vena cava. In the present study, infusion of the arginine vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine] Arg8-vasopressin into conscious dogs with chronic caval constriction did not decrease mean arterial blood pressure. However, the dose of infused antagonist completely blocked the pressor response to 2 micrograms of exogenous vasopressin. Also the antagonist produced no effect on heart rate, plasma renin activity, or urinary volume and electrolyte excretions. A slight, transient increase (P less than or equal to 0.05) was observed in creatinine clearance and in PAH clearance following antagonist infusion, suggesting a possible decrease in renal vascular resistance. These data suggest that the direct vasoconstrictor actions of vasopressin contribute minimally, if at all, to blood pressure maintenance following chronic caval constriction. Alternatively, blockade of endogenous vasopressin receptors at the level of peripheral arterioles may have resulted in no depressor response due to a masking of this response by other compensatory hormonal and neural pressor systems.     

Cardiorenal reflexes do not attenuate the renal effects of infused atriopeptin in conscious dogs.

Low-dose infusions of atriopeptin produce only a modest diuresis and natriuresis. However, these infusions also decrease atrial pressures, a change that has been postulated to elicit an antidiuretic and antinatriuretic reflex from cardiac receptors and thereby to attenuate the direct renal effects of atriopeptin. To determine whether the renal effects of intravenously administered atriopeptin might be attenuated by a cardiorenal reflex, we infused alpha-human atrial natriuretic peptide (alpha-hANP) into cardiac-denervated and sham-operated (normal) conscious dogs. Following a control period, alpha-hANP was infused into each dog at 12.5, 25, or 50 ng.kg-1.min-1 for 1 hr. Infusion of alpha-hANP at 50 ng.kg-1.min-1 produced similar decreases in left atrial pressure in both normal and cardiac-denervated dogs (peak changes, -1.6 +/- 0.8 vs -2.4 +/- 0.9 mm Hg, respectively). Increases in urine flow (peak changes, 0.13 +/- 0.05 vs 0.20 +/- 0.06 ml/min) and sodium excretion (peak changes, 56 +/- 22 vs 70 +/- 11 microEq/min) also were not different between groups. The lower doses of alpha-hANP also elicited renal and hemodynamic responses in the cardiac-denervated dogs that did not differ significantly from those in the normal dogs. These data indicate that the diuresis and natriuresis elicited by intravenously administered alpha-hANP are not attenuated by a cardiorenal reflex in conscious dogs.     

Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1).day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.     

Norepinephrine-induced atriopeptin release in conscious dogs is mediated by alterations in atrial pressure

This study was designed to determine whether the increase in atriopeptin secretion induced by an intravenous infusion of norepinephrine is mediated directly by adrenergic receptor stimulation or indirectly by the associated increase in atrial pressure. Norepinephrine was infused at 0.5 microgram.kg-1.min-1 for 30 min into both sham-operated (intact) and cardiac-denervated conscious dogs. The infusion increased mean arterial pressure in all dogs. On the other hand, left atrial pressure increased from 5.0 +/- 0.7 to 9.6 +/- 1.6 mmHg (p less than 0.01) in intact dogs, but decreased from 5.5 +/- 1.0 to 2.0 +/- 0.7 (p less than 0.01) in cardiac-denervated dogs. Right atrial pressure changes followed similar trends, but were not significant in the intact group. Plasma atriopeptin increased from 73 +/- 12 to 110 +/- 18 pg/ml (p less than 0.01) as left atrial pressure increased in intact dogs and decreased from 79 +/- 15 to 54 +/- 10 pg/ml (p less than 0.01) as left atrial pressure decreased in cardiac-denervated dogs. The changes in plasma atriopeptin correlated closely with the changes in left atrial pressure (r = 0.941, p less than 0.001) and to a lesser extent with the changes in right atrial pressure (r = 0.413, p less than 0.05). These results suggest that the change in plasma atriopeptin induced by infusion of norepinephrine into conscious dogs is mediated by the concomitant change in atrial pressures.     

Effect of head-down tilt on basal plasma norepinephrine and renin activity in humans

The effects of loading cardiopulmonary baroreceptors on basal norepinephrine and renin activity were studied in six normal subjects. Loading of cardiopulmonary baroreceptors was accomplished by a 60-min 30 degrees head-down tilt with small supplemental saline infusions. Central venous pressure was measured continuously by intrathoracic catheter; arterial pressure was measured indirectly by cuff. During the tilt, central venous pressure increased from 5.1 +/- 1.3 to 8.9 +/- 1.7 mmHg (P less than 0.001), whereas arterial pressure was unchanged. Plasma norepinephrine (185 +/- 85 pg/ml) and plasma renin activity (3.9 +/- 5.7 ng . ml-1 . h-1) did not change. Moderate sustained loading of cardiopulmonary baroreceptors is therefore without effect on unstressed plasma norepinephrine and renin activity in normal humans, suggesting that the tonic inhibitory effects of these receptors on these neurohumoral control systems are not readily increased in the basal state.     

Modulation of cardiovascular reflexes by arginine vasopressin

Arginine vasopressin (AVP), a potent vasoconstrictor, does not raise arterial pressure in normal humans or neurally intact animals, even during infusions that achieve pathophysiological plasma concentrations. It has been proposed that this is because AVP facilitates the baroreflex control of the circulation. We performed a series of investigations to test this hypothesis, and to determine sites at which AVP might act to augment the baroreflex. In anesthetized rabbits, vasopressin (36 pmol.kg-1.min-1) increased discharge from both medullated and nonmedullated single fibres from aortic baroreceptor nerves during elevations in aortic arch pressure. Similarly, vasopressin (36 pmol.kg-1.min-1) increased the response of left ventricular mechanoreceptor single fibre discharge to elevations of left ventricular end-diastolic pressure. These observations suggest that sensitization of high and low pressure baroreceptors is one mechanism by which vasopressin may facilitate baroreflexes. In a further series of experiments in sinoaortic denervated anesthetized rabbits, vasopressin (18 pmol.kg-1.min-1) facilitated vagally mediated reflex inhibition of renal sympathetic nerve activity during volume expansion. In humans, AVP (0.37 pmol.kg-1.min-1) raised plasma AVP to an antidiuretic level (22 +/- 4 fmol/mL), but did not change blood pressure or the baroreflex control of heart rate or forearm vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased thirst and vasopressin secretion after myocardial infarction in rats

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.     

Neurohumoral and cardiopulmonary response to sustained submaximal exercise in the dog

Neurohumoral, cardiovascular, and respiratory parameters were evaluated during sustained submaximal exercise (3.2 km/h, 15 degrees elevation) in normal adult mongrel dogs. At the level of activity achieved (fivefold elevation of total body O2 consumption and threefold elevation of cardiac output), significant (P less than 0.05) increases in plasma norepinephrine and epinephrine concentration (from 150 +/- 23 to 341 +/- 35 and from 127 +/- 27 to 222 +/- 31 pg/ml, respectively) were present, as well as smaller but significant increases in plasma renin activity and plasma aldosterone concentration (from 2.2 +/- 0.3 to 3.1 +/- 0.6 ng X ml-1 X h-1 and from 98 +/- 8 to 130 +/- 6 pg/ml, respectively). Plasma arginine vasopressin increased variably and insignificantly. The cardiovascular response (heart rate, systemic arterial and pulmonary arterial pressures, left ventricular filling pressure, and calculated total peripheral and pulmonary arteriolar resistance) closely paralleled that of human subjects. Increased hemoglobin concentration was induced by exercise in the dogs. The ventilatory response of the animals was characterized by respiratory alkalosis. These data suggest similarities between canine and human subjects in norepinephrine, plasma renin activity, and plasma aldosterone responses to submaximal exercise. Apparent species differences during submaximal exertion include greater alterations of plasma epinephrine concentration and a respiratory alkalosis in dogs.     

Effects of a nonperssor analogue of vasopressin on plasma renin activity and salt and water excretion in water-loaded,anesthetized dogs

The object of this study was to determine the importance of vasoconstrictor activity in the suppression of renin secretion by vasopressin. Arginine vasopressin (AVP) (0.05 and 0.1 ng/kg/min) and a nonpressor analogue of vasopressin, 1-deamino-[4-threonine, 8-D-arginine]-vasopressin (dTDAVP) (0.01 and 0.05 ng/kg/min), were infused intravenously in anesthetized hypophysectomized dogs. Neither dTDAVP nor AVP influenced arterial pressure or heart rate but both suppressed plasma renin activity. Infusion of dTDAVP at 0.01 and 0.05 ng/kg/min suppressed plasma renin activity to 86±4% (p<0.05) and 63±6% (p<0.01) of the control values respectively. Infusion of AVP at 0.05 and 0.1 ng/kg/min suppressed plasma renin activity to 60±8% (p<0.01) and 59±12% (p<0.05) of the central values respectively. dTDAVP and AVP both produced significant increases in sodium excretion. These data demonstrate that vasoconstrictor activity is not required for the effects of vasopressin on renin secretion and sodium excretion.     

Immediate baroreflex-neuroendocrine interactions in humans during graded water immersion

Healthy male subjects underwent graded water immersion for a study of arterial baroreceptors and neuroendocrine responses. Blood samples were studied for plasma renin activity, aldosterone, arginine vasopressin, norepinephrine and epinephrine. Results showed that ten minutes of immersion was enough to suppress the release of arginine vasopressin, renin, and norepinephrine. The role of baroreceptors in the release of these substances is discussed.     

Prevention of the normal expansion of maternal plasma volume: a model for chronic fetal hypoxaemia

The effects of inadequate expansion of maternal blood volume on uterine blood flow, fetal oxygen levels and vasoactive mediators during the third trimester were studied in 8 pregnant sheep. Results were compared to those obtained during 15 normal pregnancies. Prevention of the normal (20 ml/day) increase in maternal plasma volume was achieved by repeated haemorrhage and injections of furosemide. These treatments also reduced the rise in blood flow to the pregnant uterine horn that normally occurs during this period of gestation: at term flow was only 508 +/- 61 (SEM) compared to 838 +/- 83 ml/min in the control group (P greater than 0.01). This reduction in uterine blood flow caused a gradual fall in fetal PaO2, and rise in fetal levels of plasma renin activity, vasopressin, catecholamines and angiotensin II without change in pHa or base excess. Four to 5 days prior to delivery, the difference from control in PaO2 was -3.9 +/- 0.5 mmHg, plasma renin activity +2.9 +/- 1.7 ng/ml.h, vasopressin +4.2 +/- 1.1 pg/ml, catecholamines +957 +/- 145.3 pg/ml and angiotensin II +243 +/- 108.2 pg/ml. Furthermore, the fall in PaO2 and rise in vasoactive mediators that normally occur 3-5 days prior to the onset of labour was either absent (PaO2 and plasma renin activity) or blunted. Thus when expansion of blood volume during pregnancy is inadequate, blood flow to the uterus is adversely affected. This leads to various degrees of chronic fetal hypoxaemia and stimulation of vasoactive mediator systems. However, the normal stimulation of vasoactive mediator systems that occurs 3-5 days before delivery appears to be blunted. Experimental prevention of blood volume expansion during pregnancy produces an excellent model for the study of chronic mild fetal hypoxaemia.     

Peripheral mechanisms involved in the pressor and bradycardic effects of centrally administered arachidonic acid

In the current study, we aimed to determine the cardiovascular effects of arachidonic acid and peripheral mechanisms mediated these effects in normotensive conscious rats. Studies were performed in male Sprague Dawley rats. Arachidonic acid was injected intracerebroventricularly (i.c.v.) at the doses of 75, 150 or 300 microg and it caused dose- and time-dependent increase in mean arterial pressure and decrease in heart rate in normal conditions. Maximal effects were observed 10 min after 150 and 300 microg dose of arachidonic acid and lasted within 30 min. In order to evaluate the role of main peripheral hormonal mechanisms in those cardiovascular effects, plasma adrenaline, noradrenaline, vasopressin levels and renin activity were measured after arachidonic acid (150 microg; i.c.v.) injection. Centrally injected arachidonic acid increased plasma levels of all these hormones and renin activity. Intravenous pretreatments with prazosin (0.5 mg/kg), an alpha1 adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10 microg/kg), a vasopressin V1 receptor antagonist, or saralasin (250 microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to arachidonic acid (150 microg; i.c.v.) while combined administration of these three antagonists completely abolished the effect. Moreover, both individual and combined antagonist pretreatments fully blocked the bradycardic effect of arachidonic acid. In conclusion, our findings show that centrally administered arachidonic acid increases mean arterial pressure and decreases heart rate in normotensive conscious rats and the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity appear to mediate the cardiovascular effects of the drug.     

Effect of carotid or aortic baroreceptor denervation on arterial pressure during hemorrhage in conscious dogs

We studied the effect of chronically denervating aortic baroreceptors (ABR; n = 6) or carotid baroreceptors (CBR; n = 7) on mean arterial pressure (MAP) and heart rate (HR) responses to hemorrhage in the dog. Neither denervation had a significant effect on basal MAP, the variability (standard deviation) of MAP, or resting HR. However, the breakpoint of MAP (defined as the volume of blood removed when MAP fell more than 10% below control and declined monotonically thereafter) was significantly reduced in dogs with only ABR functional (12.4 +/- 1.4 ml/kg) compared with the volume in the intact condition (18.9 +/- 1.8 ml/kg). In contrast, there was no difference in the breakpoint or the MAP at any time during hemorrhage in dogs with both CBR functional compared with their intact responses. In a different group of dogs (n = 6), responses were determined with both CBR operating and again after unilateral denervation, leaving only one CBR (1CBR) functional. Basal MAP and the variability of MAP were not altered in dogs with only 1CBR functional, but the breakpoint (11.7 +/- 1.4 ml/kg) during hemorrhage was significantly different compared with responses with two CBR (21.2 +/- 2.3 ml/kg), and MAP fell to much lower levels. These results indicate that the CBR can compensate fully for loss of ABR during hemorrhage but not vice versa; and bilateral CBR inputs are required for normal responses to hemorrhage.     

Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats

Cardiovascular deconditioning occurs in astronauts after spaceflight or in individuals subjected to bed rest. It is characterized by an increased incidence of orthostatic intolerance. The mechanisms responsible for orthostatic intolerance are likely multifactorial and may include hypovolemia, autonomic dysfunction, and vascular and cardiac alterations. The arterial baroreflex is an important compensatory mechanism in the response to an orthostatic stress. In a previous study, we demonstrated that arterial baroreflex mediated sympathoexcitation was blunted in hindlimb-unloaded (HU) rats, a model of cardiovascular deconditioning. The arterial baroreflex also contributes to the regulation of vasoactive hormones including vasopressin and angiotensin II. In the present study, we tested the hypothesis that the neurohumoral response to hypotension is also attenuated in rats after 14 days of hindlimb unloading. To test this hypothesis, the vasodilator diazoxide (15 or 25 mg/kg) or saline (0.9%) was administered to produce hypotension or control conditions, respectively, in conscious HU and control rats. Plasma samples were collected and assayed for vasopressin and plasma renin activity (PRA). Diazoxide (25 mg/kg) produced significant increases in vasopressin and PRA compared with saline controls. HU rats exhibited significantly higher levels of vasopressin at rest and the increase in vasopressin levels during hypotension was enhanced by hindlimb unloading. Neither resting nor hypotension-induced PRA was altered by hindlimb unloading. These data suggest that although baroreflex-mediated sympathoexcitation is blunted by hindlimb unloading, hypotension-induced vasopressin release is enhanced and hypotension-induced PRA is unaffected. Increased circulating vasopressin may serve to compensate for blunted baroreflex regulation of sympathetic nervous activity produced by hindlimb unloading or may actually contribute to it.     

Baroreceptor-mediated suppression of osmotically stimulated vasopressin in normal humans

Increases in central venous pressure and arterial pressure have been reported to have variable effects on normal arginine vasopressin (AVP) levels in healthy humans. To test the hypothesis that baroreceptor suppression of AVP secretion might be more likely if AVP were subjected to a prior osmotic stimulus, we investigated the response of plasma AVP to increased central venous pressure and mean arterial pressure after hypertonic saline in six normal volunteers. Plasma AVP, serum osmolality, heart rate, central venous pressure, mean arterial pressure, and pulse pressure were assessed before and after a 0.06 ml.kg-1.min-1-infusion of 5% saline give over 90 min and then after 10 min of 30 degrees head-down tilt and 10 min of head-down tilt plus lower-body positive pressure. Hypertonic saline increased plasma AVP. After head-down tilt, which did not change heart rate, pulse pressure, or mean arterial pressure but did increase central venous pressure, plasma AVP fell. Heart rate, pulse pressure, and central venous pressure were unchanged from head-down tilt values during lower-body positive pressure, whereas mean arterial pressure increased. Plasma AVP during lower-body positive pressure was not different from that during tilt. Osmolality increased during the saline infusion but was stable throughout the remainder of the study. These data therefore suggest that an osmotically stimulated plasma AVP level can be suppressed by baroreflex activation. Either the low-pressure cardiopulmonary receptors (subjected to a rise in central venous pressure during head-down tilt) or the sinoaortic baroreceptors (subjected to hydrostatic effects during head-down tilt) could have been responsible for the suppression of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)