Comparative Study on Influences of Nicardipine, Diltiazem, Verapamil, Trimetazidine, Hydralazine and Propranolol on the Contraction of Isolated Guinea-Pig Vas Deferens

Abstract

Influences of nicardipine, diltiazem, verapamil, trimetazidine, hydralazine, and propranolol on the contraction of isolated guinea-pig vas deferens were compared. The contraction was induced by norepinephrine, barium chloride, calcium chloride or potassium chloride: norepinephrineand barium-induced contractions were examined in the preparation kept in Locke's solution, calcium-induced contraction in the preparation which was pretreated with tetrasodium edetate and transferred to edetate-free sucrose medium, and potassium-induced contraction in the preparation kept in a sucrose medium without edetate-pretreatment. The calcium-induced contraction was not influenced by the presence of potassium ions in the medium, slightly influenced by sodium ions and was concentration-dependent of the added calcium ions. The calciuminduced contraction was assumed to be a contraction caused by the influx of calcium ions from medium into the tissue, while potassium-induced contraction to be a contraction caused by the release of calcium in the tissue.
With either the norepine phrine- or barium-induced contraction, the calcium ions utilized for the contraction must be supplied from the calcium ions in the medium and/or calcium in the tissue. The drug, which can influence the calcium-and/or potassium-induced contraction, might influence the norepinephrine- and barium-induced contractions. The drugs, which can suppress the potassium-induced contraction at concentrations lower than 0.5μmol/1, were nicardipine, verapamil and diltiazem. The drugs, which can suppress the calcium-induced contraction at concentrations lower than 50μmol/1, were trimetazidine, diltiazem and verapamil. Nicardipine (50μmol/1), hydralazine (1.0 mmo/1) and propranol(1.0mmol/1) did not influence the calcium-induced contraction, but hydralazine ( 2.0mmol/1) suppressed both the calcium-and potassium-induced contractions. Propranolol (10μmol/1)suppressed while trimetazidine (3.0μmol/1) increased the potassium-induced contraction. Each drug concentration to suppress the norepinephrine-induced contraction was almost the same as those to suppress the barium-induced contraction. Each drug effect to influence the norepinephrineand barium-induced contractions might be probably brought about by the mixed influences of each drug on both the influx and release of calcium ions while trimetazidine did by inhibiting the leakage of calcium ions through membrane. It is noteworthy that the drugs so-called " Ca-antagonist" need each 100 times or more higher concentrations to suppress the calcium-induced contraction than those to suppress the potassium-induced contraction: this might be a common pharmacological property among their Ca-antagonistic actions.