Nitric oxide decreases [Ca2+]i in vascular smooth muscle by inhibition of the calcium current.

Endothelium derived relaxing factor (nitric oxide, or NO) activates cytoplasmic guanylate cyclase in vascular smooth muscle and decreases vascular tone through cGMP-dependent mechanisms that are not yet understood fully. In cultured vascular smooth muscle cells (A7r5 cell line) sodium nitroprusside (NP), a vasodilator that decomposes into nitric oxide, lowered [Ca2+]i in cells in which [Ca2+]i was elevated after depolarization. NP decreased current through voltage-gated calcium channels, but did not affect release of calcium from intracellular stores. Hemoglobin, a scavenger of NO, reversed the effect of NP on [Ca2+]i and 8-Br-cGMP, a membrane permeant form of cGMP, mimicked the effect of NP on [Ca2+]i and on calcium currents. Thus, the signal transduction mechanism of endothelium dependent relaxation of vascular smooth muscle involves a decrease in [Ca2+]i by inhibition of Ca2+ entry. Relaxation or vasodilation would then result from decreased activity of myosin light chain kinase, in addition to myosin light chain dephosphorylation.