Signal transduction in smooth muscle - Selected contribution: NO released to flow reduces myogenic tone of skeletal muscle arterioles by decreasing smooth muscle Ca2+ sensitivity

To clarify the contribution of intracellular Ca2+ concentration ([Ca2+](i)) dependent and -independent signaling mechanisms in arteriolar smooth muscl e (aSM) to modulation of arteriolar myogenic tone by nitric oxide (NO), rel eased in response to increases in intraluminal flow from the endothelium, c hanges in aSM [Ca2+](i) and diameter of isolated rat gracilis muscle arteri oles (pretreated with indomethacin) were studied by fluorescent videomicros copy. At an intraluminal pressure of 80 mmHg, [Ca2+](i) significantly incre ased and myogenic tone developed in response to elevations of extracellular Ca2+ concentration. The Ca2+ channel inhibitor nimodipine substantially de creased [Ca2+](i) and completely inhibited myogenic tone. Dilations to intr aluminal flow (that were inhibited by N-omega-nitro-L-arginine methyl ester ) or dilations to the NO donor S-nitroso-N-acetyl-DL-penicillamine (that we re inhibited by the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a ]quinoxalin-1-one) were not accompanied by substantial decreases in aSM [Ca 2+](i). 8-Bromoguanosine cGMP and the cGMP-specific phosphodiesterase inhib itor zaprinast significantly dilated arterioles yet elicited only minimal d ecreases in [Ca2+](i). Thus flow-induced endothelial release of NO elicits relaxation of arteriolar smooth muscle by a cGMP-dependent decrease of the Ca2+ sensitivity of the contractile apparatus without substantial changes i n the pressure-induced level of [Ca2+](i).