[Role of L-arginine--endogenous NOS inhibitors--endothelin-1 pathway for the vascular remodelling].
Mechanisms of vascular remodelling process are complex and poorly understood. We describe herein the role of L-arginine-endogenous NOS inhibitors-endothelin-1 pathway for the vascular remodelling after endothelial denudation of the rabbit carotid artery. It is reportedly known that NO is a vasodilating substance, an inhibitor of platelet aggregation and adhesion, and an inhibitor of vascular smooth muscle cell proliferation and that endothelin-1, of which production is inhibited by NO, is a potent vasoconstrictor and a potent mitogen. An accumulation of endogenous inhibitors (L-NMMA and ADMA) in regenerated endothelial cells after the endothelial denudation was accompanied by the decreased NO generation, the increased endothelin-1 content within the vessel wall and the occurrence of intimal hyperplasia. Endothelin-1 content within the vessel wall was significantly increased after the exogenous L-NMMA administration for 2 weeks, suggesting that accumulated L-NMMA results in the decreased NO generation and, in turn, increases endothelin-1 content. Endothelin-1 facilitated the [3H]-L-NMMA uptake by endothelial cell and brought about the potentiation of L-NMMA-mediated inhibition of NO generation. These results strongly suggest that the L-arginine--endogenous NOS inhibitors--endothelin-1 pathway plays an active role for vascular remodelling.
Azuma
H
H
Department of Melecular Design, Tokyo Medical & Dental University, Japan.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism*; D002339:Carotid Arteries / Q000166:cytology; D002455:Cell Division; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012038:Regeneration / Q000502:physiology; D019323:omega-N-Methylarginine / Q000378:metabolism
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase