Effect of indapamide on the electromechanical properties of rat myometrium and rat portal vein

J Mironneau, JP Savineau and C Mironneau

The effects of indapamide were studied on membrane potentials, ionic currents and isometric contractions in pregnant rat uterine smooth muscle. Indapamide (5 X 10(-6) to 10(-3) M) depressed K contractures and twitch contractions within 3 to 6 min. At a concentration of 3 X 10(-4) M, indapamide decreased the rate of rise, amplitude and rate of repolarization of the action potential and prolonged the potential duration. The inward current, carried either by Ca or Na ions, was depressed without modification of the respective reversal potentials. The decrease in K outward current was dependent on the reduction of the Ca inward current. In both myometrium and rat portal vein, indapamide depressed the transient contractions induced in Ca-free, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-containing solutions by either acetylcholine (10(-4) M) or norepinephrine (10(-6) M). In myometrium, the maintained and repetitive contractions induced by acetylcholine as well as the contractions produced by prolonged membrane depolarizations were not affected by indapamide. The results indicate that indapamide acts primarily on the plasma membrane of spontaneously active smooth muscles by reducing both inward (Ca and Na) currents and outward (K) current; it may also exert an effect to depress contractions supported by a release of Ca from the sarcoplasmic reticulum.

Volume 236, Issue 2, pp. 519-525, 02/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics