EFFECTS OF MIDAZOLAM ON CONTRACTIONS IN SMOOTH-MUSCLE OF THE RABBIT MESENTERIC-ARTERY

We investigated the undetermined effects of midazolam on agonist-induc ed contraction in vascular smooth muscle strips from the rabbit mesent eric resistance artery. Midazolam, in concentrations more than 10 mu M , attenuated norepinephrine ([NE] 0.3-10 mu M)-induced contractions in Krebs solution. The attenuating effect was more potent on the tonic a nd oscillatory responses than on the rapid phasic response. When volta ge-operated Ca2+ channels (VOC) were blocked by nifedipine, midazolam, in concentrations more than 1 mu M, attenuated both phasic and tonic responses. In Ca2+ free solution, midazolam, in concentrations more th an 1 mu M, attenuated NE-induced contractions, but not caffeine-induce d contractions. When NE and caffeine were applied successively, midazo lam attenuated NE-induced contractions, but enhanced caffeine-induced contractions. Because the attenuating effect of midazolam on NE-induce d contractions in high K+, Ca2+-free solution were not different from the effect in normal Ca2+-free solution, the attenuating effects of mi dazolam could not have been induced via membrane hyperpolarization. Th ese results indicate that midazolam attenuated the agonist-induced con tractions by inhibition of Ca2+ influx occurring not only through VOC, but also through agonist-mediated Ca2+ channels and by the inhibition of Ca2+ release from intracellular store sites.