NITROGLYCERIN RELAXES RAT TAIL ARTERY PRIMARILY BY LOWERING CA2+ SENSITIVITY AND PARTIALLY BY REPOLARIZATION

At least five mechanisms are hypothesized to account for guanosine 3', 5'-cyclic monophosphate (cGMP)-induced relaxation of arterial smooth m uscle: 1) repolarization, 2) inhibition of Ca2+ release, 3) inactivati on of L-type Ca2+ channels, 4) enhancement of Ca2+ efflux/sequestratio n, and 5) decreasing the intracellular Ca2+ concentration ([Ca2+](i)) sensitivity of force. The goal of this study was to investigate the ph ysiological relevance of these five mechanisms in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenyleph rine or high extracellular K+ concentration ([K+](o)) and then relaxed the tissue by adding nitroglycerin to increase guanosine 3',5'-cyclic monophosphate concentration. We measured membrane potential (E(m)) wi th microelectrodes, [Ca2+](i) with fura 2, and isometric force with a strain-gauge transducer. We found that decreases in the [Ca2+](i) sens itivity of force accounted for most of the nitroglycerin-induced relax ation of tissues prestimulated with maximal (1 mu M) phenylephrine or 30 mM [K+](o). In submaximally (0.1-0.3 mu M) phenylephrine-prestimula ted tissues, nitroglycerin-induced relaxation was caused primarily by a decrease in the [Ca2+](i) sensitivity of force and partially by repo larization and the resultant decrease in [Ca2+](i). Nitroglycerin also partially attenuated transient increases in [Ca2+](i) and force induc ed by 100 mu M phenylephrine in the absence of extracellular Ca2+, ind icating that nitroglycerin also inhibited intracellular Ca2+ release. Nitroglycerin-induced relaxation was not associated with inactivation of Ca2+ channels or enhancement of Ca2+ efflux/sequestration. These da ta suggest that nitroglycerin relaxes precontracted rat tail artery pr imarily by decreasing the [Ca2+](i) sensitivity of force.