David P. Brooks

Central Adrenergic Control of Vasopressin Release

The role of central adrenergic receptors in the control of vasopressin release was studied in the conscious rat. Norepinephrine (10 micrograms) and the alpha-1 agonist, phenylephrine (50 micrograms), administered intracerebroventricularly resulted in significant increases in the plasma vasopressin concentration and blood pressure. The alpha-2 agonist, BHT 933 (50 micrograms) and the beta agonist, isoproterenol (10 micrograms) both caused a significant decrease in the plasma vasopressin concentration with only small changes in blood pressure. The central administration of the alpha-1 antagonist corynanthine (20 micrograms) had no effect on the plasma vasopressin concentration; however, increases in plasma vasopressin levels were observed when either the alpha-2 antagonist yohimbine (20 micrograms) or the beta antagonist propranolol (20 micrograms) were given. It is concluded that central noradrenergic pathways may play an important role in the control of vasopressin release and that this control may involve alpha-1, alpha-2 and beta adrenoreceptors.

Vasopressin in Rats With Genetic and Streptozocin-Induced Diabetes

Rats were administered streptozocin (STZ; 50 or 75 mg/kg i.v., tail vein) or vehicle. Approximately 2 wk later, venous and arterial catheters were implanted for subsequent (24 h later) vasopressin, electrolyte, and hemodynamic measurements. STZ-induced diabetic (STZ-D) rats demonstrated a dose-dependent increase in the plasma glucose concentration, plasma osmolality, and plasma vasopressin concentration. Mean arterial blood pressure (MABP) was unchanged, but heart rate was reduced. Diabetes-prone BB rats, maintained on or withdrawn from insulin treatment for 24–48 h, and diabetes-resistant rats were instrumented and studied as above. Spontaneous-diabetes–prone rats demonstrated increases in plasma glucose concentration and plasma osmolality similar to STZ-D rats but had significantly greater plasma vasopressin concentrations. The significant decrease in MABP observed in these animals probably contributed to the enhanced vasopressin response. We conclude that both osmotic and cardiovascular parameters play important roles in vasopressin secretion in diabetic rats.

Interrelationship between central bradykinin and vasopressin in conscious rats

Intracerebroventricular administration of bradykinin (1, 5 and 20 micrograms) into conscious rats resulted in significant dose-dependent increases in the plasma vasopressin concentration, mean arterial blood pressure and heart rate. Peripheral blockade of the pressor action of vasopressin with a vasopressin pressor antagonist (10 micrograms/kg, i.v.) did not cause an attenuation but rather a potentiation and prolongation of the pressor effects of central bradykinin (20 micrograms). Central administration of the vasopressin antagonist (150 ng) caused no peripheral blockade of the pressor effects of exogenous i.v. vasopressin but almost abolished the bradykinin-induced tachycardia, with little effect on the pressor effects of central bradykinin (20 micrograms). The results indicate that centrally administered bradykinin stimulates vasopressin release into the plasma and that central vasopressin may modulate the cardiovascular actions of central bradykinin.

Sex difference in pressor responsiveness to vasopressin and baroreflex function in DOC-salt hypertensive rats.

This study was undertaken to investigate further the possible role of vasopressin in the sexual dimorphism of deoxycorticosterone (DOC)-salt hypertension. The study was carried out 3 weeks after initiating treatment with DOC and salt in uninephrectomized male and female rats. Mean arterial pressure (MAP) was lower in female than in male DOC-salt hypertensive rats (177 +/- 7 versus 198 +/- 4 mmHg; P less than 0.01). Mean arterial pressure did not differ between male and female normotensive control rats. Increases in MAP in response to graded i.v. infusions of vasopressin were markedly attenuated in female normotensive and hypertensive rats, but there was no sex difference in pressor responses to i.v. phenylephrine. Baroreflex sensitivity was reduced in both male and female DOC-salt rats, but to a greater extent in males (P less than 0.01). Diminished pressor responsiveness to vasopressin and a smaller impairment of baroreflex sensitivity may contribute to the reduced development of DOC-salt hypertension in female rats.

The Response of Vasopressin and Blood Pressure to Hemorrhage in Shr and Wky Rats

The effects of hemorrhage on plasma vasopressin levels and blood pressure were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Graded hemorrhage was produced by bleeding the rats at 10 min intervals over a total period of 65 min, to produce cumulative blood losses equivalent to 0.5, 1.0, 1.5, 2.0 and 3.0% of body weight in each animal. Hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. At cumulative reductions in blood volume equivalent to 1.0 to 3.0% of body weight, there were greater reductions in arterial pressure and greater increases in plasma vasopressin concentrations in SHR than WKY. Basal blood volume in SHR was 10% lower than in WKY. In SHR, the greater vasopressin response to hemorrhage may have been due in part to the greater fall in arterial pressure. Although the lower blood volume may have contributed to the latter, derangements in baroreceptor function may also have been important.

Cardiovascular Response to Vasopressin Vasopressor Antagonist Administration during Water Deprivation in the Rat

The cardiovascular effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injection of a selective vasopressin vasopressor antagonist, [1-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid-2-(0-methyl)tyrosine]arginine vasopressin (TMe-AVP) were examined in conscious rats under basal conditions and following 48 h of water deprivation. Pressor responses to i.v. vasopressin (50 ng/kg) were not blunted by i.c.v. treatment with either vehicle or 0.5 microgram/kg TMe-AVP. A dose of 5.0 microgram/kg TMe-AVP (i.c.v.) did reduce the pressor response to vasopressin, indicating peripheral leakage of the antagonist. Water deprivation for 48 h increased plasma vasopressin concentrations from 0.7 +/- 0.1 to 2.8 +/- 0.1 microU/ml and increased blood pressure from 112 +/- 2 to 123 +/- 1 mm Hg. No effect of the vasopressin antagonist on blood pressure could be detected following either i.c.v. (0.5 microgram/kg) or i.v. (5.0 micrograms/kg) treatment in water-deprived animals. However, a significant increase in heart rate was observed in water-deprived rats following i.v. injection of 5.0 micrograms/kg of TMe-AVP. Central vasopressin vasopressor receptor blockade appears to exert little effect on blood pressure either under basal conditions or during water deprivation. The data further delineate the relationship of plasma vasopressin concentrations to cardiovascular homeostasis.

Changes in plasma arginine vasopressin during transition from fetus to newborn following minimal trauma delivery of lambs and goats

Vasopressin in umbilical arterial and venous blood is high at delivery and may be important in the maintenance of arterial pressure and absorption of lung liquid. We used chronically instrumented near-term fetal lambs and goats to investigate the changes in plasma vasopressin that occur during perinatal cardiovascular transition following cesarean section without labor. Plasma arginine vasopressin was more than 5 times greater 15 min following birth than immediately prior to clamping the umbilicus, and it fell progressively over the ensuing 2-5 h to levels not significantly different from before birth. Fifteen min after delivery, neither arterial pressure, blood gases, nor pH appeared to account for the increase.

Effect of Vertebral Artery Infusions of Oxytocin on Plasma Vasopressin Concentration, Plasma Renin Activity, Blood Pressure and Heart Rate and Their Responses to Hemorrhage

Infusion of oxytocin into one vertebral artery of anesthetized dogs did not alter plasma vasopressin concentration, blood pressure or heart rate. However, there was a significant (p less than 0.01) increase in plasma renin activity (PRA; delta = 7.6 +/- 2.3 ng/ml X h). A 35% hemorrhage caused blood pressure to fall by 9.4 +/- 4.0 mm Hg (p less than 0.01) and PRA to rise by 8.8 +/- 2.7 ng/ml X h (p less than 0.05). In 8 dogs that were subjected to a similar hemorrhage and that also received an intravertebral infusion of oxytocin, blood pressure was maintained and PRA increased by 14 +/- 4.3 ng/ml X h (p less than 0.05). Heart rate and plasma vasopressin responses were similar in both hemorrhage groups. The results indicate that oxytocin prevented the fall in blood pressure associated with a hemorrhage, possibly by increasing renin release.

Naloxone does not improve cardiovascular or blunt vasopressin responses in spontaneously hypertensive rats following graded hemorrhage.

The effects of continuous intravenous infusion of naloxone or vehicle on the blood pressure and vasopressin responses to step-wise hemorrhage were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Step-wise hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. The WKY were relatively resistant to the hypotensive effect of hemorrhage. No significant differences were noted in blood pressure responses between naloxone-treated and vehicle-treated SHR while naloxone treatment attenuated hypotension only slightly in WKY. Plasma vasopressin levels were also elevated by naloxone treatment in SHR following a nonhypotensive hemorrhage equivalent to 0.5% of body weight. However, no differences were observed between plasma vasopressin levels in naloxone-treated and vehicle-treated SHR at greater degrees of hemorrhage. In addition, plasma vasopressin levels were similar at all times in hemorrhaged WKY, regardless of treatment. Plasma vasopressin levels were increased by naloxone in both time-control SHR and WKY. The data demonstrate that naloxone-sensitive systems exert only minimal effects on the immediate cardiovascular responses to hypovolemia in normotensive rats and no measurable effects in SHR. It does appear that naloxone-sensitive mechanisms contribute a small, but significant, tonic inhibitory influence over vasopressin secretion in both normotensive and hypertensive rats under basal conditions and in SHR in response to a small reduction in blood volume.

Effect of vertebral, carotid and intravenous infusions of lysine vasopressin on plasma vasopressin and cardiovascular function.

The cardiovascular and vasopressin-releasing effects of vertebral artery, carotid artery and intravenous (i.v.) infusions of lysine vasopressin (150 microU/kg X min) were studied in anesthetized dogs. Vertebral and carotid artery infusions of lysine vasopressin led to similar decreases in cardiac output as i.v. infusions. Heart rate, however, decreased to a greater extent with vertebral and carotid artery infusions of lysine vasopressin than i.v. infusions. There were no changes in either mean arterial blood pressure or the plasma vasopressin concentration. The results indicate that peripheral vasopressin: has a central effect to reduce heart rate; has a peripheral effect on the heart to reduce cardiac output, and probably does not feed back to inhibit its own release.