Depression of Contractions of Rabbit Aorta and Guinea Pig Vena cava by Mesudipine and Other Slow Channel Blockers

Abstract

The effects of several drugs having Ca⁺⁺-antagonistic and vasodilating properties were compared in arterial and venous smooth muscles. Developed force (phasic component) was recorded from isolated rings (about 2 mm wide) of blood vessel wall taken from rabbit aorta or guinea pig inferior vena cava. The vascular smooth muscle (VSM) was stimulated to contract for a sustained period by elevating the extracellular K⁺ concentration ([K]_o) to 100 mM or by exposure to norepinephrine (NE). All drugs depressed the K⁺-induced contractures in a dose-dependent manner between 10-9 and 10–5 M. The order of potency in aorta was: mesudipine = verapamil > diltiazem > nifedipine. Of the three drugs studied in vena cava, the order of potency was: mesudipine > verapamil > bepridil. It is concluded that, in both preparations of arterial and venous VSM, mesudipine is the most potent inhibitor of K⁺-induced contractions. Aortic contractions to 10^-7 M NE were depressed at concentrations of Ca⁺⁺ antagonists 2 or 3 orders of magnitude less than those needed to depress contractions to 10–5 M NE. The NE-induced contractions were depressed by the drugs to about the same extent as the K⁺-induced contractions when 10^-7 M NE was used, but were depressed to a much smaller extent when 10–5 M NE was used. This may reflect the involvement of intra-cellular Ca⁺⁺ storage sites in contractions induced by high NE concentrations. It is likely that these drugs depress and block Ca⁺⁺ influx through the cell membrane.