Effects of endothelins on nerve-mediated contractions of the mouse vas deferens.

The effects of 3 endothelins (ETs) on sympathetic nerve-mediated responses were investigated in the mouse isolated vas deferens. ET-1, ET-2 and, to a lesser extent, ET-3 (0.3-30 nM) caused marked and sustained potentiation of responses to field stimulation at 0.1 Hz, but had little effects, if any, on baseline tension. Incubation with nicardipine (30 nM) strongly inhibited the development of twitch potentiation by the ETs. Twitches potentiated beforehand by ET-1 (10 nM) displayed marked resistance to inhibition by nicardipine, so that 10 microM of nicardipine only reversed part of the effect of ET-1. ET-1 also enhanced both components of the response to high frequency field stimulation (2 to 16 Hz) and contractions induced by submaximal concentrations of noradrenaline, ATP or KCl. All effects of ET-1 were mimicked by Bay K 8644, an activator of L-type Ca++ channels. It is concluded that ETs increase the efficacy of sympathetic neurotransmission in the mouse vas deferens by, at least in part, a postjunctional mechanism which involves activation of L-type Ca++ channels.