Inhibition of endothelium-dependent vascular relaxation by tetrandrine

The effects of tetrandrine, a Ca2+ antagonist of bis-benzylisoquinoline alk aloid origin, on endothelium-dependent and -independent vascular responsive ness were investigated in perfused rat mesenteric artery. In endothelium-in tact preparations pre-contracted with 3 mu M phenylephrine and fully relaxe d by 0.3 mu M acetylcholine tetrandrine caused a rapid transient contractio n. In endothelium-denuded preparations, tetrandrine caused only vasorelaxat ion of phenylephrine-contraction. The biphasic effect of tetrandrine in ace tylcholine-relaxed preparations could also be mimicked by sequential applic ations of atropine/tetrandrine or N-G-nitro-L-argininemethylester (LNAME)/ tetrandrine, but atropine or L-NAME alone caused only vasoconstriction. Thi s tetrandrine-induced transient vasoconstriction was also observed in prepa rations relaxed with ATP, histamine or thapsigargin (TSG), but not those re laxed with A23187, sodium nitroprusside or nifedipine. The present results suggest that tetrandrine, in addition to its known inhibitory effects on va scular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhib its NO production by the endothelial cells possibly by blockade of Ca2+ rel ease-activated Ca2+ channels.