[Inhibition of induced contraction in the isolated rat mesenteric vascular bed by Ro 40-5967, a novel calcium antagonist].
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.
Sato
Y
Y
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Watanabe
H
H
Himori
N
N
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D020748:Mibefradil; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D016232:Endothelins; D017466:Receptors, Endothelin; D013764:Tetrahydronaphthalenes; D014665:Vasodilator Agents; D020748:Mibefradil; D009543:Nifedipine; D009638:Norepinephrine