Hemodynamic Effects of Guanethidine in Man

Abstract

Guanethidine was administered in a single intravenous infusion to supine hypertensive and normotensive subjects. Hemodynamic changes during the transient pressor phase were consistent with catechol amine effect. The later hypotensive effect occurred only in the hypertensive subjects and was usually associated with a slight decrease in cardiac output in patients without cardiac decompensation and a slight increase in output in those with congestive heart failure. Total peripheral resistance decreased although there was an increase in splanchnic vascular resistance and a decrease in the percentage of the cardiac output perfusing the hepatic-portal bed.Tests of sympathetic nervous system activity revealed that, although the Valsalva "overshoot" usually was blocked, complete inhibition of digital vasoconstrictor reflexes did not always occur and vascular responsiveness to tyramine and ephedrine was not diminished up to six hours following intravenous guanethidine. Tyramine responses were also demonstrated in a group of patients on effective long-term oral therapy with guanethidine.These studies suggest that guanethidine has unique hemodynamic effects not necessarily shared by ganglionic blocking agents, bretylium tosylate, or reserpine. Catechol amine depletion probably is not important in the mechanism of the antihypertensive and sympathetic inhibitory actions in man, and the possibility of an additional non-adrenergic effect is considered.