ANTAGONISTIC EFFECT OF YANGAMBIN ON PLATELET-ACTIVATING-FACTOR (PAF)-INDUCED CARDIOVASCULAR COLLAPSE

The cardiovascular protective effects of yangambin, a novel and specif ic naturally-occurring platelet activating factor (PAF) receptor antag onist, were investigated in the pentobarbital anesthetized and artific ially ventilated rat. Yangambin (3-30 mg kg(-1)) as well as the refere nce PAF antagonist WEB 2086 (0.1-1.0 mg kg(-1)) prevented the circulat ory collapse elicited by the intravenous administration of PAF (0.5 mu g kg(-1)), in a dose-dependent manner. Yangambin did not interfere wi th the hypotensive effect of several endogenous vasoactive mediators s uch as acetylcholine, bradykinin, histamine and serotonin. Moreover, w hen adminstered as a post-treatment the antagonist showed the ability to reverse the cardiovascular effects induced by PAF (1.0 mu g kg(-1)) . The protective effect of yangambin showed to have a duration of acti on of more than 2 hours. It is concluded that yangambin is a selective antagonist of the cardiovascular effects of PAF and therefore constit utes a potential therapeutic agent in different shock states where abn ormal PAF release is supposed to play an important role.