Objective: The effects of 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), anthracene-9-carboxylate (9-AC) (chloride channel blockers) and zaprinast (an inhibitor of phosphodiesterase-5) on endothelin-1 (ET-1) induced contractions of pregnant rat myometrium were investigated in vitro. Methods: Isolated myometrial strips were obtained from pregnant rats, and the strips were mounted in organ baths for recording of isometric tension (n = 8). The effects of 10(-7) to 10(-4) M NPPB, 10(-7) to 10(-4) M 9-AC, and 10(-7) to 10(-4) M zaprinast on 10(-8) M ET-1-induced contractions of pregnant rat myometrial smooth muscle were recorded. Results: NPPB and 9-AC increased the amplitude of ET-1-induced myometrial contractions, while decreasing the frequency, in a concentration-dependent manner. The amplitude of myometrial contractions were significantly increased by NPPB and 9-AC beginning from the concentration of 10(-6) M. The frequency of myometrial contractions were significantly decreased by NPPB and 9-AC beginning from the concentration of 10(-6) M. Zaprinast inhibited the amplitude and frequency of ET-1-induced myometrial contractions in a concentration-dependent manner. Zaprinast-induced decreases in amplitude and frequency of myometrial contractions reached statistical significance beginning from the concentrations of 10(-7) M and 10(-5) M, respectively. Conclusion: These data provide evidence that the ET-1-induced contractions of pregnant rat myometrial strips may be modulated by chloride channels. In addition, zaprinast effectively inhibited ET-1-induced contractions in pregnant rat myometrium. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.