Calcium antagonists and excitation of the vascular muscle membrane.

Several mechanisms of action for Ca2+ antagonists are possible at the vascular muscle cell membrane and at subsequent steps. In rat caudal artery, nitrendipine hyperpolarizes the resting vascular muscle cell, an action different from that of verapamil. Hyperpolarization might be expected to explain the relaxant action of nitrendipine because hyperpolarization per se causes a decrease in Ca2+ influx. SHR vascular muscle cells show a greater dependence on extracellular K+ concentration for the action of nitrendipine than WKY, as indicated by both tension and membrane potential measurements, suggesting an action on an ion pump. It is possible to directly test the hypothesis that inhibition of Ca2+ influx can directly account for the entire effect of nitrendipine by determination of intracellular Ca2+ with the metallochromic absorbence dye, arsenazo III. Nitrendipine not only decreased the magnitude of the Ca2+ signal but also enhanced the return to resting, or below resting, intracellular Ca2+ levels. Experiments on isolated single cells from the azygous vein of neonatal rats showed evidence of both blockade of Ca2+ influx and enhancement of Ca2+ efflux. These measurements suggest that nitrendipine might cause relaxation by stimulating Ca2+ efflux as well as by decreasing passive Ca2+ influx. Therefore, the action of nitrendipine might be more complicated than simply blocking Ca2+ channels, possibly involving stimulation of active ion transport.