Bepridil (CERM-1978) and Verapamil Depression of Contractions of Rabbit Aortic Rings

Abstract

Isolated rings (about 1 mm wide) of rabbit ascending aorta were stimulated to contract by norepinephrine (NE), increased extracellular potassium ion concentration, or electrical stimulation. When tested 20 min after addition, bepridil (CERM-1978) (10^–5–10^-6 M), a new antianginal agent, and verapamil (10^-5–10^–6 M) depressed the contractile responses to high K⁺ (30 mM) and NE (10^-6 M). Bepridil was almost as potent as verapamil in this action. Responses to strong electrical field stimulation were not affected by either agent. The depressed responses to NE in Ca-free or EGTA-containing solutions were not further affected by bepridil or verapamil. Contractile responses to NE obtained from depolarized tissues, however, were markedly depressed by bepridil. These results suggest that bepridil, like verapamil, acts to inhibit contractions of vascular smooth muscle by decreasing influx of extracellular Ca⁺⁺. In depolarized vascular smooth muscle, bepridil may also exert an effect to depress contractions supported by intracellular Ca⁺⁺ release.