Evidence that nitric oxide does not mediate the hyperpolarization and relaxation to acetylcholine in the rat small mesenteric artery.
1 Acetylcholine caused a concentration-dependent smooth muscle hyperpolarization and relaxation in rat small mesenteric arteries (diameter at 100 mmHg 250-450 mm) stimulated with noradrenaline (3 microM). 2 Nitric oxide (NO), generated from either NO-gas or from acidified sodium nitrite, also induced smooth muscle hyperpolarization but only in the absence of active force. However, unlike the hyperpolarizations to acetylcholine, those to NO were abolished either by prior smooth muscle depolarization caused by noradrenaline, or by the K+ channel blocker, glibenclamide (3 microM). 3 Hyperpolarization and relaxation to acetylcholine were unaffected by prior exposure of the mesenteric artery to either the cyclo-oxygenase inhibitor, indomethacin (10 microM), or the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NNA, 100 microM). 4 Haemoglobin (1.5 microM), which binds and inactivates NO, blocked the hyperpolarizing and vasorelaxant response to NO, but did not alter either response to acetylcholine. 5 These data show that, in the rat small mesenteric artery, membrane hyperpolarizations to NO and acetylcholine are mediated by different mechanisms, and that the hyperpolarizations to NO and acetylcholine are mediated by different mechanisms, and that the hyperpolarization induced by NO is not involved in the responses to acetylcholine. In addition, they provide evidence that the acetylcholine responses in this artery, which are endothelium-dependent, are not mediated by the release of NO.
Garland
C J
CJ
Baker Medical Research Institute, Victoria, Australia.
McPherson
G A
GA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology*; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
D001685:Biological Factors; D010108:Oxyhemoglobins; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin