l‐NG‐nitro arginine (l‐NOARG), a novel, l‐arginine‐reversible inhibitor of endothelium‐dependent vasodilatation in vitro

• Published in: British journal of pharmacology 1990-02, Vol.99 (2), p.408-412
• Main Authors: Moore, P.K., Al‐Swayeh, O.A., Chong, N.W.S., Evans, R.A., Gibson, A.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Cell physiology; Electric Stimulation; Endothelium, Vascular - drug effects; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Male; Mesenteric Arteries - drug effects; Molecular and cellular biology; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Nitroarginine; Nitroprusside - pharmacology; Norepinephrine - pharmacology; omega-N-Methylarginine; Phenylephrine - pharmacology; Rabbits; Responses to growth factors, tumor promotors, other factors; Vasodilation - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb14717.x

1 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). 2 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. 3 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). 4 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). 5 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. 6 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.