The effect of vasoactive antagonists in endetoxin shock

Abstract

The effect of pharmacologic antagonists on vascular pressures in the perfused splenic artery, a branch of the portal vein, and in a systemic artery were monitored for 30 minutes after the injection of an LD 50 of Shigella flexneri endotoxin. In control animals the injection of endotoxin was followed by a rapid increase in splenic arterial pressure, portal venous pressure, and vascular resistance across the spleen. Systemic arterial pressure exhibited an abrupt decline after the injection of endotoxin. Pretreatment of dogs with the alpha vascular receptor antagonist, phenoxybenzamine, prevented the increase in portal venous pressure and markedly attenuated the rise in splenic perfusion pressure. Pretreatment of dogs with either of two beta vascular receptor antagonists, Nethalide or DCI, ameliorated the fall in systemic arterial pressure without diminishing the splanchnic vascular responses to endotoxin. The serotonin antagonist, Cyproheptadine, diminished the increase in splenic perfusion pressure after endotoxin. Atropine, reserpine, Compound 48 80 , or antihistaminics did not diminish the hypotensive response to endotoxin, although the increase in portal venous pressure was less marked in dogs to which Compound 48 80 had been administered, and perfusion pressure did not increase as markedly in animals pretreated with antihistaminics.