NITRIC-OXIDE DECREASES [CA2-MUSCLE BY INHIBITION OF THE CALCIUM CURRENT(](I) IN VASCULAR SMOOTH)

Endothelium derived relaxing factor (nitric oxide, or NO) activates cy toplasmic guanylate cyclase in vascular smooth muscle and decreases va scular tone through cGMP-dependent mechanisms that are not yet underst ood fully. In cultured vascular smooth muscle cells (A7r5 cell line) s odium nitroprusside (NP), a vasodilator that decomposes into nitric ox ide, lowered [Ca2+](i) in cells in which [Ca2+](i) was elevated after depolarization. NP decreased current through voltage-gated calcium cha nnels, but did not affect release of calcium from intracellular stores . Hemoglobin, a scavenger of NO, reversed the effect of NP on [Ca2+](i ) and and 8-Br-cGMP, a membrane permeant form of cGMP, mimicked the ef fect of NP on [Ca2+](i) and on calcium currents. Thus, the signal tran sduction mechanism of endothelium dependent relaxation of vascular smo oth muscle involves a decrease in [Ca2+](i) by inhibition of Ca2+ entr y. Relaxation or vasodilation would then result from decreased activit y of myosin light chain kinase, in addition to myosin light chain deph osphorylation.