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 muscle: 1) repolarization, 2) inhibition of Ca2+ release, 3) inactivation of L-type Ca2+ channels, 4) enhancement of Ca2+ efflux/sequestration, and 5) decreasing the intracellular Ca2+ concentration ([Ca2+]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 (Em) with microelectrodes, [Ca2+]i with fura 2, and isometric force with a strain-gauge transducer. We found that decreases in the [Ca2+]i sensitivity of force accounted for most of the nitroglycerin-induced relaxation of tissues prestimulated with maximal (1 microM) phenylephrine or 30 mM [K+]o. In submaximally (0.1-0.3 microM) phenylephrine-prestimulated tissues, nitroglycerin-induced relaxation was caused primarily by a decrease in the [Ca2+]i sensitivity of force and partially by repolarization and the resultant decrease in [Ca2+]i. Nitroglycerin also partially attenuated transient increases in [Ca2+]i and force induced by 100 microM phenylephrine in the absence of extracellular Ca2+, indicating 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 data suggest that nitroglycerin relaxes precontracted rat tail artery primarily by decreasing the [Ca2+]i sensitivity of force.
Chen
X L
XL
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Rembold
C M
CM
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D005996:Nitroglycerin; D002118:Calcium