Vascular pharmacodynamics of NG-nitro-L-arginine methyl ester in vitro and in vivo.
The inhibitory effects of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodilatation were studied in conscious rats and isolated rat aortic rings. In phenylephrine (PE, ED90)-preconstricted aortae, L-NAME caused prolonged and complete inhibition of acetylcholine (ACh)-induced relaxation with IC50 of 4 x 10(-7) M and Hill coefficient (n) of 1. The inhibition was abolished by L-arginine (L-Arg), independently of whether it was applied 10 min earlier or 4 hr later than L-NAME. Intravenous bolus injection of L-NAME caused prolonged increases in mean arterial pressure (MAP), with Emax of 50 +/- 7 mm Hg, ED50 of 5 +/- 1 x 10(-6) mol/kg and n of 2. Intravenous infusion of L-Arg shifted the dose-MAP curve of L-NAME to the right without changing Emax or n. A modified Schild plot (n = 2) for the action of L-NAME gave a slope not different from unity, suggesting that L-Arg inhibits competitively the MAP response of L-NAME. Intravenous infusion of ACh decreased MAP in rats treated with L-NAME (4.8 x 10(-5) mol/kg) or PE. Compared to PE-treated rats, L-NAME inhibited the depressor response to ACh by 50%. Thus, a dose of L-NAME 10 times its ED50 in raising MAP only partially blocked the depressor responses to ACh.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Poon
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Pang
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D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009599:Nitroprusside; D010656:Phenylephrine; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester