S. Yamaguchi et al., EFFECTS OF MIDAZOLAM ON CONTRACTIONS IN SMOOTH-MUSCLE OF THE RABBIT MESENTERIC-ARTERY, Anesthesia and analgesia, 84(1), 1997, pp. 199-205
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.