Depression of contractions of rabbit aorta and guinea pig vena cava by mesudipine and other slow channel blockers.

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 greater than diltiazem greater than nifedipine. Of the three drugs studied in vena cava, the order of potency was: mesudipine greater than verapamil greater than 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 intracellular 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.