Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric artery

We investigated the undetermined effects of midazolam on agonist-induced contraction in vascular smooth muscle strips from the rabbit mesenteric resistance artery. Midazolam, in concentrations more than 10 μM, attenuated norepinephrine ([NE] 0.3-10 μM)-induced contractions in Krebs solution. The attenuating effect was more potent on the tonic and oscillatory responses than on the rapid phasic response. When voltage-operated Ca 2+ channels (VOC) were blocked by nifedipine, midazolam, in concentrations more than 1 μM, attenuated both phasic and tonic responses. In Ca 2+ -free solution, midazolam, in concentrations more than 1 pM, attenuated NE-induced contractions, but not caffeine-induced contractions. When NE and caffeine were applied successively, midazolam attenuated NE-induced contractions, but enhanced caffeine-induced contractions. Because the attenuating effect of midazolam on NE-induced contractions in high K + , Ca 2+ -free solution were not different from the effect in normal Ca 2+ -free solution, the attenuating effects of midazolam could not have been induced via membrane hyperpolarization. These results indicate that midazolam attenuated the agonist-induced contractions by inhibition of Ca 2+ influx occurring not only through VOC, but also through agonist-mediated Ca 2+ channels and by the inhibition of Ca 2+ release from intracellular store sites.