L-ARGININE INDUCES RELAXATION OF RAT AORTA POSSIBLY THROUGH NON-ENDOTHELIAL NITRIC-OXIDE FORMATION

1 The relaxation of rings of rat thoracic aorta induced by L-arginine and its derivatives was investigated. 2 L-Arginine (0.3-100-mu-M), 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. 3 L-Arginine methyl ester, N-alpha-benzoyl L-arginine and L-homo-arginine had essentially similar effects to those of L-arginine. 4 N(G)-nitro L-arginine methyl ester (L-NAME, 3-mu-M), N(G)-nitro L-arginine (L-NNA, 1-mu-M) and N(G)-monomethyl L-arginine (L-NMMA, 10-mu-M), inhibitors of nitric oxide (NO) formation from L-arginine, inhibited or reversed the L-arginine-induced relaxation, irrespective of the presence of absence of the endothelium. In contrast, N(G)-nitro D-arginine was without effect. 5 Haemoglobin (Hb, 10 nM) and methylene blue (MB, 0.3-mu-M) inhibited or reversed the L-arginine-induced relaxation. 6 L-Arginine (1-100-mu-M), 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-mu-M), MB (1-mu-M) and L-NAME (100-mu-M). Removal of the endothelium did not significantly alter the L-arginine-induced cyclic GMP production. 7 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.