Nitroglycerin relaxes rat tail artery primarily by lowering Ca2+ sensitivity and partially by repolarization
Chen, X.L.; Rembold, C.M.
American Journal of Physiology 271(3 Pt 2): H962-H968
1996
ISSN/ISBN: 0002-9513 PMID: 8853330 Document Number: 462833
At least five mechanisms are hypothesized to account for guanosine 3',5'-cyclic monophosphate (cGMP)-induced relaxation of arterial smooth muscle: 1) repolarization, 2) inhibition of Ca-2+ release, 3) inactivation of L-type Ca-2+ channels, 4) enhancement of Ca-2+ efflux/sequestration, and 5) decreasing the intracellular Ca-2+ concentration ((Ca-2+)-i) sensitivity of force. The goal of this study was to investigate the physiological relevance of these five mechanisms in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine 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) with microelectrodes, (Ca-2+)-i with fura 2, and isometric force with a strain-gauge transducer. We found that decreases in the (Ca-2+)-i sensitivity of force accounted for most of the nitroglycerin-induced relaxation of tissues prestimulated with maximal (1 mu-M) phenylephrine or 30 mM (K+)-o. In submaximally (0.1-0.3 mu-M) phenylephrine-prestimulated tissues, nitroglycerininduced relaxation was caused primarily by a decrease in the (Ca-2+)-i sensitivity of force and partially by repolarization and the resultant decrease in (Ca-2+)-i. Nitroglycerin also partially attenuated transient increases in (Ca-2+)-i and force induced by 100 mu-M phenylephrine in the absence of extracellular Ca-2+, indicating that nitroglycerin also inhibited intracellular Ca-2+ release. Nitroglycerin-induced relaxation was not associated with inactivation of Ca-2+ channels or enhancement of Ca-2+ efflux/sequestration. These data suggest that nitroglycerin relaxes precontracted rat tail artery primarily by decreasing the (Ca-2+)-i sensitivity of force.