Mechanisms of the bepridil-induced vasodilation of the rabbit mesenteric artery.

Bepridil, at a concentration over 10 microM, increased the membrane resistance and, over 20 microM, depolarized the smooth muscle membrane of the rabbit mesenteric artery. These changes in membrane properties may be due to inhibition of K and possibly Cl conductances, as examined by the current-voltage relationship. The spike potential evoked by current pulses in the presence of 3 mM tetraethylammonium or from the excitatory junction potential (e.j.p.) was somewhat inhibited by bepridil (over 10 microM). Bepridil (over 5 microM) reduced the amplitude of e.j.p. without changing the facilitation process of e.j.ps and, at concentrations beyond 20 microM, it inhibited the facilitation of e.j.ps. Bepridil (over 0.1 microM) inhibited and over 1 microM blocked completely the tonic response of the K-induced contraction. Thus, the voltage-dependent Ca channels activated by K-induced depolarization and during the spike generation differ in nature. Bepridil inhibited the caffeine-induced contraction in intact muscles and the Ca-induced contraction in skinned muscles prepared by saponin to the same extent, but more effectively inhibited the norepinephrine-induced contraction without altering the norepinephrine-induced depolarization. We conclude that bepridil mainly inhibits the voltage-dependent Ca channel (the K depolarization sensitive) in smooth muscle membrane. High concentrations of bepridil (over 10 microM) inhibit the Ca spike, the K and Cl conductances, contractile proteins and Ca release from intracellular stored sites of smooth muscle cells and Ca mobilization at nerve terminals. Actions of bepridil differ from those of other Ca antagonists.