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.

The Effect of Guanethidine and Propranolol on Capillary Blood Flow in Subcutaneous Tissue and Muscle in Essential Hypertension

“…This finding is in general agreement with reports which suggest inhibition of sympathetic vasoconstrictor mechanisms by guanethidine [1,4] and sub sequent decrease in total peripheral vascular resistance in hypertensive subjects [4,12,13,23], It would appear, however, that this vasomotor effect is not generalized, since guanethidine causes a simultaneous reduc tion in capillary flow in forearm muscle. The fact that guanethidine practi cally eliminated the differences between untreated hypertensives and healthy controls suggests that the hemodynamic pattern of hypertension involves an increased sympathetic tone which is 'neutralized' by guanethidine with a return to a normal distribution pattern of local tissue blood flows.…”

Assessment of Autonomic and Non-Autonomic Components of Resting Hindlimb Vascular Resistance and Reactivity to Pressor Substances in Renal Hypertensive Rabbits

“…In previous studies in hypertensive man and animals the rise in vascular resistance has been reported to be due to changes in non-autonomic factors and increased autonomic constrictor tone (Mendlowitz & Touroff, 1952;Conway, 1963;Cohn, Liptak & Freis, 1963;Korner, Shaw, Uther, West, McRitchie & Richards, 1973). However, in all these studies measurements after block have been made at a lower blood pressure than before block (Cohn et al, 1963;Korner et al, 1973;Tarazi & Dustan, 1973).…”

“…However, in all these studies measurements after block have been made at a lower blood pressure than before block (Cohn et al, 1963;Korner et al, 1973;Tarazi & Dustan, 1973). This will alter transmural pressure, local chemical substances controlling vascular resistance and possibly circulating hormones.…”

Hemodynamics of Early Experimental Renal Hypertension in Dogs

“…The decreased femoral venous compliance we observed in hypertensive dogs is not acutely altered by several antihypertensive agents, including propranolol and guanethidine, which are thought to lower blood pressure at least in part by decreasing cardiac output (26,27). Thus this study provides no evidence that these agents act acutely via increases in venous compliance, at least in dogs with perinephritic hypertension.…”