Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.
To investigate the mechanism underlying increased endothelin-1 (ET-1) release in diabetic rats, we administered L-arginine chronically to streptozotocin (STZ)-induced diabetic rats. The plasma concentrations of glucose, ET-1 and NOx (NO2- + NO3-) were all significantly raised at 10 weeks after the STZ injection. Chronic administration of L-arginine resulted in a significantly higher plasma NOx concentration and a significantly lower plasma ET-1 level at 10 weeks compared with the untreated diabetic group. ET-1 induced a biphasic vasodilator/vasoconstrictor response in the perfused isolated mesenteric arterial beds from all groups. The vasodilatation was significantly greater in diabetic rats than in age-matched controls. Chronic oral L-arginine administration had no significant effect on the enhanced ET-1-induced vasodilatation seen in the untreated diabetic rats. The vasoconstrictions induced by ET-1 and methoxamine were significantly attenuated in STZ-diabetic rats. The attenuated vasoconstrictor response to ET-1, but not that to methoxamine, was further attenuated by chronic treatment with L-arginine. We conclude that since chronic L-arginine administration not only reduced the increase in plasma ET-1 levels but also further attenuated the ET-1-induced vasoconstriction without affecting the change in vasodilatation, chronic L-arginine administration could be valuable for the treatment of the symptoms of diabetic mellitus related to ET-1.
Makino
Ayako
A
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Kamata
Katsuo
K
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D001120:Arginine; D008729:Methoxamine