In our previous study, econazole caused a decrease in serum nitrite levels in septic mice in vivo, but it enhanced the mortality rate. The aim of the study was to investigate the in vitro effects of econazole on receptor-operated and depolarization-induced contractions on endothelium-intact and -denuded rat isolated aorta. Econazole (0.1, 1 and 10 mu M) significantly inhibited receptor-operated (phenylephrine, Phe) and depolarization (KCl)-induced contractions of endothelium-intact or -denuded rings in a noncompetitive and concentration-dependent manner. Removal of endothelium changed the pD'(2) values only for KCl-induced responses. The pD'(2) values of L-type calcium channel blocker nifedipine were significantly higher than the econazole on Phe concentration-response curves in endothelium-intact and -denuded rings. Econazole caused a biphasic response in precontracted by Phe or KCI in endothelium-intact and -denuded rings, first a transient contraction following sustained relaxation. Removal of endothelium did not affect the contractile responses induced by Phe. The contractile responses induced by 10 mu M econazole in the KCI-precontracted rings were antagonized by the treatment of a-adrenergic receptor antagonist, phentolamine (10 mu M). Deendothelization was significantly increased the IC50 values of econazole obtained from Phe- and KCl-precontractions. The relaxations induced by 10 mu M econazole in endothelium-intact rings precontracted with Phe or KCl were not changed by NO synthase inhibitor, L-N-G-nitroarginine (100 mu M). The IC50 values of econazole were significantly higher than nifedipine in endothelium-intact and -denuded rings. These results suggest that econazole is a noncompetitive antagonist on alpha(1)-adrenoceptor-mediated and depolarization-induced contractions in rat isolated aorta by inhibiting Ca2+ entry through L-type calcium channels, and the endothelium seems to modulate vascular responses induced by this agent. The vascular effects of econazole may limit the usage of this agent in septic shock. (C) 2000 Elsevier Science Inc. All rights reserved.