NG-nitro-L-arginine contracts vascular smooth muscle by an endothelium-independent mechanism.
We characterized the contractile effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) in endothelium-denuded rat aortic rings. Incubation with L-NNA (4 x 10(-6)-6.4 x 10(-5) M) for 5 h dose-dependently contracted endothelium-denuded aortic rings. In contrast, incubation with NG-nitro-D-arginine (D-NNA 6 x 10(-6)-4 x 10(-4) M), diphenyleneiodonium (DPI, NO synthase inhibitor, 3.2 x 10(-6) M) or dexamethasone (10(-7) M, inhibitor of expression of inducible NO synthase) did not contract the denuded rings. The L-NNA-induced contraction was not significantly altered by the presence of the endothelium or by pretreatment with L-arginine (L-Arg 2 x 10(-3) M) or lipopolysaccharide (100 ng/ml). These results suggest that L-NNA causes slow contraction of endothelium-denuded vascular smooth muscle (VSM) by a mechanism independent of the inhibition of constitutive or inducible NO biosynthesis.
Wang
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Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
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D000818:Animals; D001011:Aorta / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D048288:Imidazolines; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines; D048288:Imidazolines; D008070:Lipopolysaccharides; D019335:Nitroarginine; D003907:Dexamethasone; D001120:Arginine; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline