The effect of l-NG-nitro arginine (l-NOARG) was compared with that of l-NG-monomethyl arginine (l-NMMA) on vasodilatation of the isolated aorta of the rabbit and perfused mesentery of the rat in response to acetylcholine (ACh) and sodium nitroprusside (NP).
l-NOARG (1.5–100 μm) and l-NMMA (3–100 μm) produced concentration-related contraction of the rabbit aorta precontracted with phenylephrine (700–900 nm). Similarly, l-NOARG (10–200 μm) and l-NMMA (30–100 μm) elevated perfusion pressure of the noradrenaline (NA, 0.6–2.5 mm)-preconstricted rat mesentery preparation.
l-NOARG (1.5–100 μm) and l-NMMA (3–100 μm) caused concentration-related inhibition of the vasodilator effect of ACh (0.01–1.0 μm) on the rabbit aorta without influencing responses to NP (0.03–0.5 μm). l-NOARG methyl ester (30 μm) also inhibited ACh-induced vasorelaxation with similar potency to NOARG. l-arginine (30–150 μm) but not d-arginine (100 μm) caused graded reversal of the inhibitory effect of both l-NOARG (15 μm) and l-NMMA (30 μm). Complete reversal of the effect of both inhibitors was achieved with 150 μm l-arginine. l-Alanine (50 μm), l-arginosuccinic acid (5 μm), l-citrulline (50 μm), l-methionine (50 μm) and l-ornithine (50 μm) failed to reverse the inhibitory effect of l-NOARG (15 μm).
l-NOARG (10–200 μm) and l-NMMA (30–100 μm) inhibited the vasodilator effect of ACh (0.006–18.0 nmol) in the rat mesentery without affecting vasodilatation due to NP (1.1–11.1 nmol). l-Arginine (100 μm) but not d-arginine (100 μm) produced partial reversal of the effect of l-NOARG (30 μm) and l-NMMA (30 μm).
l- and d-Nα-butyloxycarbonyl NG-nitro arginine (100 μm) produced modest (approximately 20%) inhibition of the effect of ACh on the rabbit aorta; this effect was not reversible with l-arginine (100 μm). l-Nα-monocarbobenzoxy arginine (l-NMCA, 50 μm), l-Nα-NG-dicarbobenzoxy arginine (l-NDCA, 5 μm) and l-NG-tosyl arginine (50 μm) were inactive.
These results identify l-NOARG as a potent, l-arginine reversible inhibitor of endothelium-dependent vasodilatation. The available data suggests that l-NOARG, like l-NMMA, inhibits endothelial nitric oxide (NO) biosynthesis.