Hypotension during vasopressin receptor blockade: role of V2 receptors and sympathetic nervous system

Abstract

This study investigated possible mechanisms for the hypotension produced by nitroprusside infusion in conscious dogs pretreated with a V1 vasopressin antagonist. The hypothesis that an action of vasopressin at V2-like receptors contributes to the hypotension was tested by comparing the effects of a V1 antagonist to the effects of a combined V1/V2 antagonist. Nitroprusside infusion produced dose-dependent decreases in arterial and atrial pressures. Larger decreases in pressures were produced in animals pretreated with either antagonist; however, the decreases in V1/V2-blocked dogs were not less than the decreases in V1-blocked dogs. These data suggest that V2-like actions of vasopressin do not contribute to the hypotensive effects of V1 blockade. A second hypothesis was that the greater hypotension was due to activation of a cardiac reflex to cause withdrawal of sympathetic tone, a decrease in peripheral resistance, and adrenal activation. Measurement of cardiac output revealed that the larger decreases in arterial pressure were due to larger decreases in total peripheral resistance. The hypotension was also associated with decreases in heart rate, unchanging plasma norepinephrine concentration, and increases in epinephrine concentration. These data are consistent with the hypothesis that the fall in pressure observed in dogs pretreated with a V1 antagonist is secondary to a decrease in peripheral resistance that is due at least in part to withdrawal of sympathetic tone.