Vasopressin and angiotensin II in reflex regulation of heart rate: effect of water deprivation

This study tested the hypothesis that endogenous angiotensin II (ANG II) and vasopressin enhance baroreflex-mediated increases in heart rate in water-replete dogs and in dogs water deprived to chronically elevate plasma ANG II and vasopressin concentrations. The baroreflex was assessed by examining the heart rate response to infusion of increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1). The effect on the baroreflex of pretreating the dogs with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or a combined V1/V2-vasopressin antagonist, alone or in combination, was determined. Nitroprusside infusion produced dose-dependent increases in heart rate, and the heart rate response was greater in water-deprived dogs in association with higher plasma levels of ANG II and vasopressin than in water-replete dogs. ANG II blockade alone depressed reflex increases in heart rate in water-deprived but not water-replete dogs. In both water-replete and water-deprived dogs, blockade of V1-vasopressin receptors reduced the heart rate response to hypotension, but this effect could be produced only when ANG II receptors were also blocked. In addition, administration of saralasin and the V1/V2-vasopressin antagonist led to a further reduction of the reflex tachycardia. These data suggest that endogenous vasopressin, acting at both V1- and V2-receptors, can amplify the increase in heart rate produced by hypotension. In addition, the results further support a physiological role for chronic elevations in endogenous ANG II in the maintenance of normal baroreflex function.

Haemodynamic Profile of Angiotensin II Antagonism in Essential Hypertensive Patients

1. The haemodynamic response to antagonistic (10 μg min−1 kg−1) and agonistic (40 μg min−1 kg−1) doses of saralasin was studied in young essential hypertensive patients. Blood pressure behaviour alone was thought to be inadequate to describe the response pattern. 2. Pre-saralasin setting of the renin-angiotensin axis was varied with salt intake (15 and 290 mmol of Na+/day) each for 10 days. This failed to influence blood pressure or plasma volume. 3. Antagonist blockade after low salt lowered blood pressure in three patients with the highest plasma renin values. Cardiac output rose in two of these, but it dropped in all others. 4. Decreases in cardiac output occurred with both doses of saralasin and even with suppression of the renin-angiotensin axis. This response is therefore unlikely to be due to removal of myocardial or venous angiotensin effects. 5. The renin-angiotensin system played a part in maintenance of blood pressure only with severe salt restriction and in a small proportion of cases. 6. No heart rate effect was seen with saralasin. 7. Blood pressure and total peripheral resistance responses were dependent on pre-(antagonist/ agonist) setting, but heart rate and cardiac output were not influenced by this factor.