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We designed a study to investigate the effect of the non-dihydropyridine calcium antagonist Ro 40-5967 in the isolated rat mesenteric vascular bed and compared it with that of nifedipine. Ro 40-5967 (10(-6) M) suppressed the KCl-induced contractions, with a potency similar to that of nifedipine (10(-7) M). A bolus injection of norepinephrine and a periarterial nerve stimulation associated with the mesenteric artery increased the perfusion pressure. Ro 40-5967 (10(-6) M) significantly inhibited the contractions induced by norepinephrine and the contractions of the stimulated periarterial nerve in the rat mesenteric arterial bed. In contrast, nifedipine (10(-7) M) did not affect these contractile responses. A subthreshold concentration of endothelin-1 potentiated the contractile responses to norepinephrine and the periarterial nerve stimulation. Ro 40-5967 (10(-6) M) prevented the potentiation of the responses to norepinephrine and the periarterial nerve stimulation evoked by endothelin-1, whereas nifedipine (10(-7) M) did not affect this augmentation. Compared to the effects of nifedipine (10(-7) M), we conclude that Ro 40-5967 (10(-6) M) more effectively prevents the contractions induced by norepinephrine and stimulation of the periarterial nerve and furthermore prevents the amplification of these contractions by endothelin-1. Ro 40-5967 does not seem to block the L-type calcium channel and exerts its effect via some other mechanism.

Inhibition of induced contraction in the isolated rat mesenteric vascular bed by Ro 40-5967, a novel calcium antagonist.