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 microM, attenuated norepinephrine ([NE] 0.3-10 microM)-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 Ca2+ channels (VOC) were blocked by nifedipine, midazolam, in concentrations more than 1 microM, attenuated both phasic and tonic responses. In Ca(2+)-free solution, midazolam, in concentrations more than 1 microM, 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 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.
Yamaguchi
S
S
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Japan.
Kanmura
Y
Y
Yoshimura
N
N
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008874:Midazolam / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D018686:Anesthetics, Intravenous; D002121:Calcium Channel Blockers; D006993:Hypnotics and Sedatives; D002110:Caffeine; D009543:Nifedipine; D008874:Midazolam; D011188:Potassium; D009638:Norepinephrine