Effects of YM-12617, an alpha adrenoceptor blocking agent, on electrical and mechanical properties of the guinea-pig mesenteric and pulmonary arteries.

The effects of YM-12617 on the electrophysiological properties of smooth muscle membranes and prejunctional nerve terminals and contractions evoked by different procedures were studied using guinea-pig mesenteric and pulmonary arteries. In concentrations over 1 nM, YM-12617 inhibited the depolarization induced by norepinephrine in both muscle tissues. Yohimbine had no effect whereas prazosin inhibited the norepinephrine-induced depolarization to a lesser extent than YM-12617. When YM-12617, in concentrations over 1 microM, was applied to the mesenteric artery the amplitude of the first excitatory junction potential evoked by a train stimulation of perivascular nerves was inhibited, but the facilitation of excitatory junction potentials evoked by frequencies over 0.1 Hz was enhanced. As a consequence, the amplitude of the excitatory junction potentials after completion of the facilitation exceeded the control, as was expected to occur with a typical alpha-2 adrenoceptor blocker. YM-12617 inhibited the contraction evoked by exogenously applied norepinephrine or perivascular nerve stimulation, with a higher potency than seen with prazosin, but this agent had no effect on the contraction evoked by excess concentrations of K+ or by direct muscle stimulation. These results indicate that YM-12617 possesses a more potent alpha-1 adrenoceptor blocking action than does prazosin, and is more selective for alpha-1 than for alpha-2 adrenoceptors.