Chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid and anthracene-9-carboxylic acid inhibit contractions of pregnant rat myometrium in vitro

OBJECTIVE: We compared in vitro relaxant effect of chloride channel modulators, such as 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and anthracene-9-carboxylate (9-AC), and beta(2)-adrenergic agonists, such as ritodrine, in pregnant rat myometrium. METHODS: Isolated myometrial strips were obtained from eight pregnant rats, and the strips were mounted in organ baths for recording isometric tension. The effects of 10(-8)-10(-4) M ritodrine, 10(-6)-3 x 10(-4) M NPPB, and 10(-6)-10(-3) M 9-AC on spontaneous contractions were recorded. RESULTS: Ritodrine (10(-8)-10(-5) M) completely inhibited the amplitude and frequency of spontaneous contractions in myometrial strips isolated from pregnant rats in a concentration-dependent manner, but the relaxant effect of ritodrine at 10(-4) M concentration resulted in tachyphylaxis. The chloride channel blocker NPPB (10(-6)-3 x 10(-4) M) and the chloride transport inhibitor 9-AC (10(-5)-10(-3) M) decreased the amplitude of spontaneous myometrial contractions in a concentration-dependent manner; the maximum inhibition produced by the highest tested concentration of each drug was 43.8% and 42.1% of the original degree of spontaneous contractions, respectively. The frequency of myometrial contractions was significantly inhibited by NPPB and 9-AC beginning with the concentration of 10(-4) M. CONCLUSION: NPPB and 9-AC appear to be effective relaxants of pregnant rat myometrium. These effects of NPPB and 9-AC might be therapeutically advantageous in clinical management of preterm labor.