AJP - Heart and Circulatory Physiology, Vol 242, Issue 3 325-H336, Copyright © 1982 by American Physiological Society
Effects of diltiazem on smooth muscles and neuromuscular junction in the mesenteric artery
H. Suzuki, T. Itoh and H. Kuriyama
Effects of diltiazem on membrane properties, neuromuscular transmissions,
and mechanical responses were investigated in intact and skinned muscles of
the guinea pig mesenteric artery. Diltiazem (greater than 10(-6) M)
depolarized the membrane, increased the membrane resistance, and suppressed
the spike evoked by either electrical depolarization or summation of
excitatory junction potentials (EJPs). This drug also suppressed the
facilitation process of amplitudes of EJPs produced by repetitive
perivascular nerve stimulations. These suppressions of EJPs were not caused
by a reduced number of active nerves contributing to the generation of EJP
but but rather to a reduction in the release of chemical transmitters.
Norepinephrine (NE)-induced and K-induced contractions were suppressed by
diltiazem noncompetitively, but the contraction evoked in Na-deficient
solution was not suppressed, i.e., diltiazem is not a nonselective
inhibitor of the Ca influx. In the saponin-treated skinned muscles
diltiazem did not suppress the release from or the accumulation into the Ca
store site, nor did it suppress activation of the Ca receptor in
contractile proteins. These results indicate that diltiazem acts on the
surface membrane and nerve terminal as a Ca antagonist or Ca-channel
blocker.
