The inhibitory effect of newer calcium antagonists (nimodipine and PY-108-068) on vasoconstriction in vivo mediated by postsynaptic alpha 2-adrenoceptors.

In the pithed rat, stimulation of postsynaptic alpha 1 as well as alpha 2-adrenoceptors is known to cause vasoconstriction. The two newer nifedipine-related calcium antagonistic agents nimodipine and PY-108-068 proved potent inhibitors of pressor responses induced by the selective alpha 2-receptor agonist B-HT 920. The maximal pressor effect of B-HT 920 was significantly reduced, whereas the hypertensive effects brought about by selective postsynaptic alpha 1-adrenoceptor stimulation were, but slightly, impaired by nimodipine and PY-108-068 and the maximal increase in diastolic pressure was not affected by the calcium antagonists. Under beta-blockade and suppression of alpha 1-adrenoceptor-mediated vasoconstrictor effects by prazosin, the resulting alpha 2-adrenoceptor-induced vasopressor response to (-)-norepinephrine proved also very sensitive towards the inhibitory action of nimodipine and PY-108-068. In comparison with nifedipine, PY-108-068 was 3.9 and nimodipine 5.1-times more potent with respect to reducing vasopressor responses of B-HT 920.