l‐Arginine induces relaxation of rat aorta possibly through non‐endothelial nitric oxide formation

Abstract

The relaxation of rings of rat thoracic aorta induced by l‐arginine and its derivatives was investigated. l‐Arginine (0.3–100 μm), but not d‐arginine, induced relaxation of the arteries, which was detectable after 2 h and maximal after 4–6 h on its repeated application; it was endothelium‐independent. l‐Arginine methyl ester, Nα‐benzoyl l‐arginine and l‐homo‐arginine had essentially similar effects to those of l‐arginine. NG‐nitro l‐arginine methyl ester (l‐NAME, 3 μm), NG‐nitro l‐arginine (l‐NNA, 1 μm) and NG‐monomethyl l‐arginine (l‐NMMA, 10 μm), inhibitors of nitric oxide (NO) formation from l‐arginine, inhibited or reversed the l‐arginine‐induced relaxation, irrespective of the presence or absence of the endothelium. In contrast, NG‐nitro d‐arginine was without effect. Haemoglobin (Hb, 10 nm) and methylene blue (MB, 0.3 μm) inhibited or reversed the l‐arginine‐induced relaxation. l‐Arginine (1–100 μm), but not d‐arginine, increased guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) levels in the tissues that relaxed in response to l‐arginine. This effect of l‐arginine was suppressed by Hb (3 μm), MB (1 μm) and l‐NAME (100 μm). Removal of the endothelium did not significantly alter the l‐arginine‐induced cyclic GMP production. These results suggest that l‐arginine itself caused a slowly developing relaxation of rat aorta, possibly via formation of NO by an endothelium‐independent mechanism. 1991 British Pharmacological Society