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Contribution of both nitric oxide and a change in membrane potential to acetylcholine‐induced relaxation in the rat small mesenteric artery
Author(s) -
Waldron Gareth J.,
Garland Christopher J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13154.x
Subject(s) - acetylcholine , medicine , repolarization , endocrinology , nitric oxide , chemistry , hyperpolarization (physics) , membrane potential , vasodilation , nitric oxide synthase , potassium channel , biophysics , electrophysiology , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
1 Acetylcholine stimulated repolarization and relaxation in isolated segments of rat small mesenteric artery (D 100 = 325 ± 9 μm) in which the smooth muscle cells were depolarized and contracted by submaximal concentrations of noradrenaline (0.75–2.5 μ m ). There was no significant difference either in the time taken to initiate relaxation or hyperpolarization, or for these parameters to reach maximum in response to acetylcholine. 2 The nitric oxide synthase inhibitor, N G ‐nitro l ‐arginine methyl ester ( l ‐NAME, 100 μ m ) reduced the pD 2 for acetylcholine‐induced relaxation from 7.5 to 7 and depressed the maximum relaxation from 89% to 68% in tissues stimulated with noradrenaline. The pD 2 for smooth muscle repolarization in these experiments was also reduced (7.4 to 6.6) but the maximum change in membrane potential in response to acetylcholine was unaltered. The increase in potential now clearly preceded relaxation by 3.7 s (to initiation) and 4.7 s (to maximum). 3 In the presence of noradrenaline and a raised potassium concentration (25 m m ), the repolarization to acetylcholine was markedly attenuated. Simultaneous tension measurements also revealed a marked reduction in the maximal relaxation to acetylcholine, but the pD 2 was unchanged at 7.4. 4 The residual relaxation recorded in the absence of marked repolarization (in the presence of noradrenaline and 25 m m potassium) was abolished by the addition of 100 μ m l ‐NAME. 5 Nitric oxide gas in solution (0.2–2.2 μ m ; NO g ) relaxed artery segments precontracted with noradrenaline. The magnitude of relaxation to NO g was not altered in the presence of noradrenaline and 25 m m potassium. 6 These data provide additional evidence that acetylcholine‐evoked endothelium‐dependent increases in membrane potential provide a major mechanism for smooth muscle relaxation in the mesenteric artery. They also show that voltage‐dependent and independent (initiated by NO) mechanisms can both contribute to relaxation, and suggest that NO may modulate the increase in membrane potential or the release of a hyperpolarizing factor.