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 microM), 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. NG-nitro L-arginine methyl ester (L-NAME, 3 microM), NG-nitro L-arginine (L-NNA, 1 microM) and NG-monomethyl L-arginine (L-NMMA, 10 microM), 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. 5. Haemoglobin (Hb, 10 nM) and methylene blue (MB, 0.3 microM) inhibited or reversed the L-arginine-induced relaxation. 6. L-Arginine (1-100 microM), 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 microM), MB (1 microM) and L-NAME (100 microM). 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.
Moritoki
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Ueda
H
H
Yamamoto
T
T
Hisayama
T
T
Takeuchi
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains
D006454:Hemoglobins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester