NITRIC-OXIDE IS AN AUTOCRINE FEEDBACK INHIBITOR OF VASCULAR SMOOTH-MUSCLE CONTRACTION

Background, Substances that increase intracellular calcium ([Ca2+](i)) , such as potassium chloride and serotonin, are known to induce vascul ar smooth muscle (VSM) contraction. One form of nitric oxide synthase, which converts L-arginine to nitric oxide, exists as a Ca2+-calmoduli n dependent enzyme. The objective of this study was to determine wheth er agonists that induce VSM contraction by increasing [Ca2+](i) might also activate Ca2+-calmodulin dependent nitric oxide synthase in VSM. Methods, Strips of bovine carotid arterial smooth muscle denuded of en dothelium were equilibrated in a physiologic muscle bath. A maximal co ntractile response to high extracellular potassium chloride and seroto nin was established. The strips were then preincubated with N-G-monome thyl-L-arginine (L-NMMA), a structural analog of L-arginine and specif ic inhibitor of nitric oxide synthase, and again treated with either K Cl or 5-hydroxytryptamine. Results. The contractile responses of muscl e strips to KCI or 5-hydroxytryptamine were significantly greater in m uscle strips pretreated with L-NMMA than responses in the absence of L -NMMA (p < 0.02, Student's t test). To determine whether this response was Ca2+ dependent, phorbolester-induced contractions in Ca2+-free co nditions were examined. No difference was noted in the magnitude of Ca 2+-free, phorbol ester-induced contractions in the presence and absenc e of L-NMMA. Conclusions. These data thus suggest that Ca2+-calmodulin dependent nitric oxide synthase is functionally present in VSM and ma y function as an autocrine regulatory mechanism of VSM contraction.