System and organ-selectivity of smooth muscle relaxants on in vitro spontaneously contracting preparations.

The effects of verapamil, papaverine and octylonium bromide on amplitude and frequency of spontaneous contractions of rabbit duodenum and rat colon, portal vein and right atria have been investigated. Myogenic nature of spontaneous contractions was demonstrated by their resistance to tetrodotoxin (100 micrograms/ml) and hexamethonium (10(-4) M). Verapamil (10(-7) - 5 X 10(-6) M) reduced, in a concentration-dependent manner, amplitude and frequency of spontaneous contractions with a certain degree of selectivity for duodenal preparations. Automaticity of rat right atria was affected by concentrations of verapamil higher than those required to modify automaticity of intestinal preparations. Papaverine (3 X 10(-6) - 3 X 10(-4) M), was almost equipotent in reducing the amplitude of spontaneous contractions of each preparation but inhibited the frequency of contractions in the following order: colon greater than duodenum greater than atrium. Octylonium bromide (10(-6) - 10(-4) M) was characterized by its greater effectiveness in reducing frequency and amplitude of spontaneous contractions of rat colon as compared to the other preparations. All three smooth muscle relaxant drugs, in spite of concentration-related reduction in amplitude, determined a parallel enhancement of frequency of spontaneous contractions in rat portal vein. Differences in drug selectivity are discussed in terms of different roles played by various Ca++-dependent processes (which constitute the cellular target of action of these smooth muscle relaxant drugs) in the genesis of frequency and amplitude of myogenic contractions in the various preparations.