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)     

Effect of 1-desamino-8-D-arginine vasopressin (DDAVP) on vasopressin release and blood pressure during hemorrhage.

Whether or not 1-desamino-8-D-arginine-vasopressin (DDAVP) reduces blood pressure or affects the release of arginine vasopressin (AVP) and renin is controversial, although evidence suggests AVP and renin are important in maintaining blood pressure during hemorrhage. We therefore investigated the effect of DDAVP on endogenous release of AVP and renin and on blood pressure during hemorrhage in dogs. In the control group the hemorrhage was performed at a rate of 0.4 ml.kg-1.min-1 for 40 min from the femoral artery. The plasma AVP concentration and renin activity (PRA) increased progressively in response to the hemorrhage, from 7.5 +/- 0.5 to 40.3 +/- 7.3 pg.ml-1, and from 11.8 +/- 1.5 to 20.5 +/- 4.2 ng.ml-1.h-1, respectively, while blood pressure decreased slightly. In the DDAVP group, intravenous infusion of DDAVP (2.5 ng.kg-1.min-1 for 40 min) and hemorrhage were simultaneously performed. The plasma DDAVP concentration increased progressively to 218 +/- 21.0 pg.ml-1. There was no significant difference, however, between the control and DDAVP groups in the response of AVP, PRA and blood pressure. The results suggested that DDAVP may not affect the release of AVP and renin or blood pressure during hemorrhage.     

Effect of vasopressin and V1 receptors blockade on hypotensive action of ANP in normotensive (WKY) and spontaneously hypertensive rats.

The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR.     

Effects of arginine vasopressin on blood pressure and renal prostaglandin E2 in rabbits.

The role of arginine vasopressin (AVP) in blood pressure regulation in humans and animals is still controversial. The present study was designed to investigate the effects of AVP on blood pressure and the excretion of sodium and prostaglandin (PG) E2 in rabbits. AVP dissolved in 0.01 M acetic acid was infused subcutaneously at a rate of 0.86 ng/kg/min with a miniosmotic pump into 12 New Zealand white rabbits (2.7-3.4 kg), while 10 controls were given vehicle alone. AVP infusion resulted in a 3.5-fold rise in the level of plasma AVP (21.8 +/- 4.4 (SEM) pg/ml) as compared with controls, associated with a significant decrease in the urine volume and urinary excretion of sodium. The PGE2 excretion was increased 1.8-fold after AVP infusion. In the chronic AVP-infused group, blood pressure was not significantly increased, but the acute vascular response to AVP was significantly attenuated without any changes in the vasopressor response to angiotensin II. Preadministration of V1-antagonist completely abolished the vasopressor action of AVP, but not that of angiotensin II, in either group. These results suggest that circulating AVP within physiological range of concentrations may stimulate renal PGE2 synthesis and attenuate the vascular response through vascular V1 receptors without affecting the baroreflex, which may be attenuated through V2 receptors.     

Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 microgram X kg-1 X min-1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 microgram X kg-1 X min-1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 microgram X kg-1 X min-1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 microgram X kg-1 X min-1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.     

Central endothelin: effects on vasopressin and the arterial baroreflex in doxorubicin heart failure rats

Endothelin 1 (ET-1) is increased in heart failure, both in plasma and within the central nervous system. Centrally, ET-1 induces sympathetic hyperactivity and arginine vasopressin (AVP) secretion. Both sympathetic activity and AVP secretion are regulated by the arterial baroreflex, which is typically impaired in heart failure. We hypothesized that central blockade of ETA receptors (ETAR) alters the baroreflex response of heart rate, renal sympathetic nerve activity (RSNA), and plasma AVP levels in a cardiomyopathic model of heart failure. Female Sprague-Dawley rats received weekly intraperitoneal injections of doxorubicin 2.5 mg x kg(-1) (doxorubicin heart failure, doxo-HF) or saline vehicle (control). After 8 weeks, they were instrumented, conditioned to the study environment, and then studied in the awake, non-restrained state. Baseline mean arterial pressure (MAP), RSNA, and plasma osmolality were similar in both groups, but heart rate (p<0.02), left ventricular pressure (p<0.001), and plasma AVP (p<0.01) were higher in the doxo-HF group. ET-1 dose dependently increased MAP, but the rise was significantly attenuated in doxo-HF rats at all doses. Baseline baroreflex control of heart rate and RSNA was similar in both groups. ETAR blockade with 4 nmol BQ123 i.c.v. significantly decreased both the upper plateau (p<0.05) and the range (p<0.05) of the baroreflex response of both heart rate and RSNA in doxo-HF but not in control rats. Despite higher basal plasma levels of AVP, ET-1 evoked a rise in plasma AVP of 13.6+/-3.2 pg x mL(-1) in doxo-HF compared with 0.4+/-0.4 pg x mL(-1) in control rats (p<0.001). To account for the blunted pressor response to ET-1 in the doxo-HF rats, gain of AVP release was calculated as DeltaAVP/DeltaMAP and was also found to be significantly greater in the doxo-HF rats (p<0.001). BQ123 prevented the rise in AVP and restored the gain in doxo-HF rats to that seen in controls. Thus, central ETAR contribute to the sympathoexcitation and AVP responses observed in heart failure due to doxorubicin cardiomyopathy.     

Counteraction of aortic baroreflex to carotid sinus baroreflex in a neck suction model.

Although neck suction has been widely used in the evaluation of carotid sinus baroreflex function in humans, counteraction of the aortic baroreflex tends to complicate any interpretation of observed arterial pressure (AP) response. To determine whether a simple linear model can account for the AP response during neck suction, we developed an animal model of the neck suction procedure in which changes in carotid distension pressure during neck suction were directly imposed on the isolated carotid sinus. In six anesthetized rabbits, a 50-mmHg pressure perturbation on the carotid sinus decreased AP by -27.4+/-4.8 mmHg when the aortic baroreflex was disabled. Enabling the aortic baroreflex significantly attenuated the AP response (-21.5+/-3.8 mmHg, P<0.01). The observed closed-loop gain during simulated neck suction was well predicted by the open-loop gains of the carotid sinus and aortic baroreflexes using the linear model (-0.43+/-0.13 predicted vs. -0.41 +/-0.10 measured). We conclude that the linear model can be used as the first approximation to interpret AP response during neck suction.     

Effects of different angiotensins during acute,double blockade of the renin system in conscious dogs

Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol.kg-1.min-1) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol.kg-1.min-1). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 +/- 19 and 274 +/- 13 ml.kg-1.min-1, respectively) than for ANG II (107 +/- 13 ml.kg-1.min-1). ANG II increased ANG IR by 60 +/- 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 +/- 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 +/- 2 to 33 +/- 2 ml/min), sodium excretion (50 +/- 7 to 16 +/- 4 micromol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 +/- 8 to 19 +/- 3 micromol/min) and aldosterone secretion (to 268 +/- 71 pg/ml) at much lower ANG IR increments ( approximately 1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved.     

Influence of baroreflex on volume elasticity of heart and aorta in the rabbit

Optimal ventriculoaortic coupling includes tuning of elastic properties. The ratio of effective arterial elastance and left ventricular endsystolic elastance is often taken as a measure for mechanical and energetical efficiency. The present study determined the time course of ventricular and aortic volume elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by using changes of eigenfrequency of two catheter-transducer systems under closed chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex response, as induced by pressure changes applied to the carotid sinus. Long-term changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol feeding). The time course and mean values of ventricular and aortic VE were changed by the baroreflex stimulus. Cholesterol feeding diminished the response. The degree of ventriculoaortic coupling, as quantified by VE(Aorta)/VE(Ventricle) ratio, varied during a single ejection period. The large span allows either maximal energetical efficiency or maximal stroke work. Although normal rabbits adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol-fed rabbits failed to do so.     

Inhibition by angiotensin II of some vasopressin effects on renal function in sheep.

The effects of intravenous infusions of arginine vasopressin (AVP) alone and with angiotensin II (AII) on renal function were studied in conscious Merino ewes. AVP at 11.5 pmol.min-1 caused an increase in water and electrolyte output which was associated with a rise in glomerular filtration rate (GFR), solute clearance, solute-free water reabsorption and tubular sodium reabsorption. Addition of AII of 100 ng.min-1 generally reversed all of these effects. The filtration fraction, which rose during AVP infusion, increased further when AII was added due to a greater fall in renal plasma flow than in GFR. The diuretic and electrolyte-excreting effects of infused AVP appeared to be brought about by an increase in GFR. It is suggested that this inappropriate effect of AVP, which is secreted in response to water deprivation, could be countered by the simultaneous production of AII.     

Effects of naloxone on systemic and regional hemodynamic responses to exercise in dogs

To determine whether endogenous opiates have a role in circulatory regulation during mild to moderate exercise, 11 chronically instrumented dogs were exercised on a treadmill up a 6% incline at 2.5 and 5.0 mph, each for 20 min, after treatment with either the opiate receptor antagonist naloxone (1 mg/kg bolus and 20 micrograms.kg-1.min-1 infusion) or normal saline. Naloxone increased plasma beta-endorphin and adrenocorticotropic hormone at rest but had no effect on resting heart rate, aortic pressure, cardiac output, left ventricular time derivative of pressure (dP/dt) and ratio of dP/dt at a developed pressure of 50 mmHg and the developed pressure (dP/dt/P), or plasma catecholamines. Plasma beta-endorphin and adrenocorticotropic hormone increased during exercise. In addition, graded treadmill exercise produced proportional increases in heart rate, cardiac output, aortic pressure, left ventricular dP/dt and dP/dt/P, and blood flow to exercising muscles, right and left ventricular myocardium, and adrenal glands. However, there were no differences in the circulatory responses to exercise between animals receiving naloxone and normal saline. Thus the endogenous opiate system probably does not play an important role in regulating the systemic hemodynamic and blood flow responses to mild and moderate exercise.     

Effect of vasopressin on myocardial capillary recruitment and coronary blood flow in the anesthetized rabbit.

The effects of infusion of arginine vasopressin (20 mU.kg-1.min-1) on coronary blood flow and the proportion of the coronary microvasculature perfused was studied in rabbit myocardium. Fluorescein isothiocyanate--dextran was injected into anesthetized open-chest rabbits to identify the perfused vessels and an alkaline phosphatase stain was employed to locate the total microvasculature. Coronary blood flow (radioactive microspheres) was studied in separate groups of rabbits. Vasopressin infusion caused bradycardia (243 +/- 19 to 165 +/- 22 beats/min, mean +/- SD) and an increase in mean blood pressure (92 +/- 18 to 104 +/- 12 mmHg) (1 mmHg = 133.32 Pa). Coronary blood flow decreased significantly with vasopressin from 209 +/- 68 to 97 +/- 36 mL.min-1.100 g-1. The proportion of the arteriolar bed per millimeter squared perfused decreased significantly after vasopressin from 54 +/- 13 to 44 +/- 21%, while the percentage of capillaries per millimeter squared increased significantly from 57 +/- 6 to 67 +/- 11%. There were no subepicardial versus subendocardial differences in any measured parameter. Thus, both coronary blood flow and the proportion of the arteriolar bed perfused decreased with vasopressin. However, compensation occurred in that the proportion of capillaries perfused increased. This indicated an independent level of control of the coronary arteriolar and capillary beds. These microvascular changes may help to maintain oxygen supply-demand balance with vasopressin in the heart.     

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.     

Somatostatin inhibits bombesin-induced effects on migrating myoelectric complexes in the small intestine of the rat

The effect of i.v. infusions of bombesin and somatostatin, administered either separately or in combination, on migrating myoelectric complexes (MMCs) in the small intestine were studied in conscious, fasted rats. The myoelectrical activity was recorded by means of three bipolar electrodes chronically implanted into the duodenum and jejunum. Infusion of bombesin (0.5, 0.9 and 3 pmol . kg-1 . min-1) interrupted the MMC and induced irregular spiking activity similar to that observed on feeding. Only after the highest dose a consistent inhibition of the MMCs and a significant increase (P less than 0.05) of the spiking activity were achieved at all recording levels. Somatostatin (90 pmol . kg-1 . min-1) did not interrupt the MMC, but reduced significantly the incidence of the activity fronts and spiking activity of the MMCs (P less than 0.05). The effects of bombesin (3 pmol . kg-1 . min-1) on the MMC pattern were inhibited by simultaneous infusion of somatostatin (P less than 0.05). In a second series of experiments, using anesthetized rats, infusion of bombesin (0.5 and 3 pmol . kg-1 . min-1) increased the plasma concentration of neurotensin- gastrin-like immunoreactivities in a dose-dependent manner. The results show that bombesin alters the myoelectrical activity of the small intestine from a fasting to a fed pattern. Since the effect of bombesin was inhibited by the hormone release inhibitor somatostatin, it is suggested that the effect of bombesin on MMC may be secondary to the release of gastrointestinal peptides, such as neurotensin or gastrin.     

Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans

During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (-9 to -24 mmHg) from between 30 and 31 +/- 1 to 34 +/- 1 mm (P < 0.05). The increase in PP from 38 +/- 2 to 44 +/- 2 mmHg (P < 0.05) was sustained during the posture change but only increased during the initial 5 min of negative pressure breathing from 36 +/- 3 to 42 +/- 3 mmHg (P < 0.05). Aortic transmural pressure decreased during the posture change and increased during negative pressure breathing. Plasma AVP was suppressed to a lower value during the posture change (from 1.5 +/- 0.3 to 1.2 +/- 0.2 pg/ml, P < 0.05) than during negative pressure breathing (from 1.5 +/- 0.3 to 1.4 +/- 0.3 pg/ml). Plasma norepinephrine was decreased similarly during the posture change and negative pressure breathing compared with seated control. In conclusion, the results are in compliance with the hypothesis that during maneuvers with similar cardiac distension, suppression of AVP release is dependent on the increase in PP and, furthermore, probably unaffected by static aortic baroreceptor stimulation.     

The cardiac contractile function and hemodynamic control in rats after chronic adriamycin treatment

Cardiac contractile function and hemodynamic parameters of control and adriamycin-treated (2 mg/kg once a week for 10 weeks) rats were studied both in the anesthetized (hexenal, 20 mg/kg) and conscious state. Radiolabelled microspheres (diameter, 15 microns) were used to measure systemic and regional hemodynamics. No significant differences between the control and adriamycin-treated groups in cardiac contractile function, total peripheral resistance, and regional blood flow (except muscles) was found in anesthetized animals. In the conscious state, a significantly higher (+70%) total peripheral resistance combined with lower blood flow in the skin and spleen was observed in adriamycin-treated rats. The response of the heart rate to changes in the arterial pressure induced by nitroglycerin and phenylephrine injection was greatly diminished after adriamycin treatment. Isoprenaline (0.64 micrograms.kg-1.min-1) increased left ventricular contractile indices approximately twofold and heart rate by 30% in the control group, while in adriamycin-treated rats only minor changes in these parameters were observed. However, cardiac output rose by 36% and total peripheral resistance fell by 36% in these animals. Results show that prolonged adriamycin treatment leads to decreased inotropic response to beta-adrenoceptor stimulation and reduced baroreflex control. These changes occur in the stage preceding congestive heart failure.     

Endothelin-1 in hypertension in the baroreflex-intact SHR: a role independent from vasopressin release

This study sought to identify whether central endothelin (ET) receptor activation contributes to the elevated pressure in spontaneously hypertensive rats (SHR) and whether an ET-stimulated vasopressin (AVP) release mediates the increased pressure. In Wistar Kyoto (WKY) rats, intracerebroventricular ET-1 induced a dose-dependent pressor response that was shifted rightward in SHR. ET(A) antagonism decreased mean arterial pressure in baroreflex-intact SHR (P<0.01), consistent with inhibition of endogenous ET-1, and blocked the pressor response to exogenous ET-1 in both strains. ET-1 increased AVP only after sinoaortic denervation (P<0.05). Contrary to WKY, sinoaortic denervation was required to elicit a significant pressor response with 5 pmol ET-1 in SHR. Sinoaortic denervation permitted ET-1 to increase AVP in both strains, and peripheral V(1) blockade decreased pressure in denervated but not intact rats. After nitroprusside normalized pressure in SHR, the pressor and AVP secretory responses paralleled those in WKY. Thus endogenous ET(A) receptor mechanisms contribute to hypertension, independent of AVP, in baroreflex-intact SHR. Although blunted in the hypertensive state, the arterial baroreflex buffers the ET-1-induced pressor and AVP secretory responses in both strains.     

The role of aortic chemoreceptors during acute anemia

The importance of aortic chemoreceptors in the circulatory and metabolic responses during acute anemia was studied in anesthetized dogs. Data were obtained from nine dogs in which the aortic chemoreceptors were surgically denervated prior to induction of anemia, and from seven sham-operated dogs. Cardiac output (QT), limb blood flow (QL), limb and whole body oxygen uptake (VO2) were determined at normal hematocrit (Hct) and at 30 min of anemia (Hct = 13%) produced by isovolemic dextran-for-blood exchange. At 30 min of anemia, QT was increased from 91 to 186 mL . kg-1 . min-1 (p less than 0.01) and from 99 to 153 mL . kg-1 . min-1 (p less than 0.01) in the sham and denervated groups, respectively. The increase in QT during anemia was less (p less than 0.05) in the aortic-denervated series. Limb flow was also increased during anemia in both groups (p less than 0.01); the mean value of 89 mL . kg-1 . min-1 in the denervated group was less than that of 130 mL . kg-1 . min-1 observed in the sham animals (p less than 0.05). Whole body VO2 decreased (p less than 0.05) in the denervated group at 30 min of anemia; limb VO2 was maintained at the preanemic control value in both groups. The data indicate that during acute anemia the aortic chemoreceptors contribute to the increase in QT.     

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.     

Effects of intravenous infusions of vasopressin and angiotensin II on central and peripheral noradrenergic function in conscious rabbits

Vasopressin (AVP) and angiotensin II (AII) are proposed to exert part of their cardiovascular effects via different actions within the central nervous system. These peptides are also known to alter central noradrenergic function. In the present study we determined the effects of these peptides administered intravenously on norepinephrine (NE) turnover in discrete brain regions thought to be involved in the regulation of circulation, and simultaneously, in various peripheral tissues. An index of NE turnover was determined by measuring the decline in tissue NE concentration 75 min after administration of alpha-methyl tyrosine (240 mg . kg-1 . min-1, i.p.). During NE synthesis blockade, five separate groups of rabbits were infused intravenously (1 h) with either saline, AVP (4 and 16 mU . kg-1 . min-1), AII (0.1 microgram . kg-1 . min-1), or phenylephrine (PE) (5 micrograms . kg-1 . min-1). The low dose of AVP produced an increased index of NE turnover in the median preoptic area and the paraventricular nucleus, and concomitantly, a decreased index of NE turnover in kidney and skeletal muscle. In contrast, AII produced an increased index of NE turnover in the locus ceruleus and the intestine. Neither the infusion of vehicle nor the infusion of phenylephrine, which increased arterial pressure comparable to AVP and AII, produced detectable changes in indices of central and peripheral norepinephrine turnover. A higher dose of AVP produced a different pattern of changes in NE turnover than the low dose. These results demonstrate that intravenous infusion of the low dose of AVP produced changes in noradrenergic function in specific central areas known to be involved in autonomic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)