Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein.

The effects of the novel anti-hypertensive agent BRL 34915, (+/-) 6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-b enzo[b]pyran-3-ol, have been compared with those of verapamil on rat isolated portal vein. BRL 34915 produced a concentration-dependent reduction in mechanical responses to noradrenaline but had relatively little inhibitory effect on K+-induced contractions. Verapamil reduced the magnitude of both noradrenaline and K+-induced mechanical responses. BRL 34915 delayed the appearance of the reduced noradrenaline contractions, a property not shared by verapamil. BRL 34915 abolished spontaneous electrical and mechanical discharges and hyperpolarized the portal vein cells close to their calculated potassium equilibrium potential. Verapamil inhibited spontaneous electrical and mechanical discharges, effects associated with a small depolarization. BRL 34915 produced a significant increase in the 86Rb efflux rate coefficient whilst verapamil was without effect on this parameter. The inhibitory effects of BRL 34915 were rapid in onset and readily reversible by washing, whilst those of verapamil were slower in onset and only slowly reversible. It is concluded that the inhibitory effects of BRL 34915 in rat portal vein are produced by the opening of potassium channels in the smooth muscle cells. This inhibits spike activity and in sufficient concentration holds the membrane potential at or close to the potassium equilibrium potential, thereby reducing the effects of excitatory agents.