Abstract

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)