Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study on rabbit aorta

Effect of cocaine on vascular enclothelium relaxing properties and the rela ted mechanism were investigated in vitro in rabbit aorta. Several vasorelax ing agents with different mechanisms, i.e. acetylcholine, substance P, calc ium ionophore A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprussid e, were employed. Cocaine effects on the vascular response to relaxing agen ts in cumulative (acetylcholine, substance P, or A23187) or single dose (2, 5-di-tert-butyl-hydroquinone) were performed in endothelium-intact aortic r ings precontracted with phenylephrine. Relaxing activity of cumulative dose s of sodium nitroprusside was evaluated in endothelium-denuded aortic rings , in the presence of cocaine. Cocaine significantly reduced endothelium-dep endent relaxations induced by acetylcholine, or substance P. By contrast A2 3187 endothelium-mediated relaxation as well as endothelium-independent rel axation by sodium nitroprusside were unaffected by cocaine. Furthermore, co caine significantly increased endothelium-dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic Ca2+-ATPase pump inhibitor, i n the aortic rings. These findings indicate that cocaine reduces nitric oxi de release from vascular enclothelium apparently through the inhibiting act ion of Ca2+-ATPase pump. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.