ANGIOTENSIN BLOCKING ACTIONS OF GUANCYDINE

¹ Department of Experimental Pharmacology, Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

Infusions of graded amounts of angiotensin to rats evoked a sustained dose-related elevation in mean blood pressure. Oral administration of guancydine two hours prior to the start of the infusion reduced the angiotensin responses. In contrast, adrenergic neuron blocking agents and ganglionic blocking agents enhanced the vasopressor actions of angiotensin. Guancydine also reduced the vasopressor response to infusions of renin, norepinephrine and, to a lesser degree, epinephrine. In nephrectomized rats, the drug caused hypotension but failed to block anglotensin responses. The angiotensin blocking action of guancydine was diminished when the drug was given repeatedly to rats, but the hypotensive and phenethylamine-blocking actions appeared unaltered. Renal and carotid blood flows and mean blood pressure were measured simultaneously in anesthetized dogs before and after injections of angiotensin and epinephrine. Vasoconstriction of the renal bed normally elicited by angiotensin was reduced after an infusion of guancydine. The vasoconstrictor response to i.a. administration of angiotensin was partially blocked, and the response to i.v. injections was converted to an increase in renal blood flow. In dogs pretreated with reserpine, injections of angiotensin and epinephrine reduced renal and carotid blood flows during the control period and increased blood flows after guancydine.