Tolerance to ethanol in the rat vas deferens. Effect of a calcium channel antagonist.

Previous research from this laboratory indicated that ethanol dose-dependently depressed vas deferens contractions. The experiments described here examine the role calcium plays in the inhibitory action of ethanol in this tissue. Rat vas deferens tissues obtained from control (dextrin maltose) or chronically ethanol-treated animals were stimulated in the absence and then in the presence of 181 mM ethanol and/or a calcium channel blocker. Increasing the extracellular calcium concentration from 2.1 to 5.0 mM decreased ethanol's in vitro inhibitory effect on contractions induced by norepinephrine, KCl or electrical stimulation. Following chronic in vivo ethanol administration, increasing the calcium concentration to 5 mM blocked this inhibition. Nifedipine, a calcium channel antagonist inhibited vas deferens contractions. In the presence of nifedipine, in vitro ethanol further depressed vas deferens contractions stimulated by norepinephrine, K+ and by electrical stimulation. In vivo ethanol treatment attenuated ethanol's inhibition in vitro, and reduced the blocking effect of the calcium antagonist on mechanical responses of the vas in ethanol-free medium. These data suggest that changes in calcium mobilization are involved in both the acute action of ethanol and the development of tolerance.