Effects of sodium nitroprusside on cytosolic calcium level in vascular smooth muscle

The inhibitory effect of sodium nitroprusside on the cytosolic Ca2+ level ([Ca2+]cyt), measured simultaneously with contraction by means of a fluorescence dye, fura-2, and on the 45Ca2+ uptake was tested in the isolated rat aortic smooth muscle. Norepinephrine increased muscle tension, 45Ca2+ uptake and [Ca2+]cyt. In a Ca2+-deficient solution, norepinephrine transiently increased muscle tension and [Ca2+]cyt. Sodium nitroprusside inhibited all changes induced by norepinephrine although the inhibition of [Ca2+]cyt was less than that of muscle contraction. Sodium nitroprusside also inhibited the high K+-induced contraction at concentrations higher than those needed to inhibit norepinephrine-induced contraction. Inhibition of the high K+induced contraction was accompanied by a small decrease in [Ca2+]cyt and a smaller decrease in 45Ca2+ uptake. Methylene blue antagonized, and M&B 22,948 potentiated the inhibitory effect of sodium nitroprusside. These results suggest that sodium nitroprusside has multiple sites of action. At relatively low concentrations, sodium nitroprusside could inhibit the Ca2+ influx and Ca2+ release. At relatively high concentrations, this inhibitor could also augment Ca2+ sequestration and decrease the sensitivity of contractile elements to Ca2+.