In vitro and ex vivo inhibitory effects of L- and D-enantiomers of NG-nitro-arginine on endothelium-dependent relaxation of rat aorta.
The in vitro and ex vivo inhibitory effects of NG-nitro-L-arginine (L-NNA) and NG-nitro-D-arginine (D-NNA) on endothelium-dependent relaxations were studied in rat aortic rings. L-NNA (3 x 10(-7) to 3 x 10(-5) M) but not D-NNA (3 x 10(-6) to 3 x 10(-4) M) induced contraction of resting aortic rings and potentiated phenylephrine-induced contraction in a concentration-dependent manner. In phenylephrine-preconstricted aortic rings, L-NNA (3 x 10(-7) to 3 x 10(-5) M) and D-NNA (3 x 10(-6) to 3 x 10(-4) M) concentration-dependently inhibited the relaxation response to acetylcholine (ACh) with similar efficacies and IC50 values of 10(-6) and 3.9 x 10(-5) M, respectively. In addition, both L-NNA (3 x 10(-5) M) and D-NNA (3 x 10(-4) M) almost totally inhibited the relaxation of preconstricted rings by the calcium ionophore A 23187. The inhibitory effects of L- and D-NNA remained for at least 4 hr after the preparations were washed out. Neither the inhibitory effects of L- and D-NNA on ACh-induced relaxation nor the ACh-induced relaxation itself were affected by pretreatment with indomethacin. However, pretreatment (10 min) or post-treatment (1 hr later) with L-Arg (10(-3) M) completely prevented or markedly reversed the inhibitory effects of L- and D-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
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Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Poon
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Pang
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D009599:Nitroprusside; D019335:Nitroarginine; D000001:Calcimycin; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin