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- Title
Rabbit aortic endothelial dysfunction by low-density lipoprotein is attenuated by L-arginine, L-ascorbate and pyridoxine.
- Authors
Yong Ji; Yi Han; Jianxin Diao, Tudor M.; Yan Huang; Qi Chen; Ferro, Albert
- Abstract
1 We investigated the relative effectiveness of L-arginine. l.-ascorbate and pyridoxine in preventing the impairment of endothelium-mediated vasorelaxation induced by native low-density lipoprotein (nLDL) from healthy subjects, oxidised LDL. (oxLDL. formed by oxidation of nLDL) or nLDL from type II diabetic patients (dLDL). 2 Rabbit aortic rings were exposed to nLDL. dLDL or oxLDL (50-200mg protein[sup-1]), or corresponding vehicle, following which they were constricted with noradrenaline 10 [sup6] M; concentration relaxation curves were determined to acetylcholine (ACH), A23187, or sodium nitroprusside (NP), in the absence or presence of L-arginine (10[sup-5]-10[sup-3]M), L-ascorbate (10[sup-5]-10[sup-3] M) pyridoxine (0.5-2.0mM). 3 nLDL. dLDL and oxLDL all inhibited relaxant responses to ACh and A23187, but not to NP, in a concentration-dependent manner (oxLDL > dLDL > nLDL). 4 In the presence of all LDL preparations,L-arginine. I -ascorbate or pyridoxine each improved ACh and A23187 responses, although none completely normalised endothelium-dependent relaxations. The maxima] effect of L-arginine occurred; 10[sup-4] M. The combination of L-arginine 10[sup-4] M, L-ascorbate 10[sup-5] and pyridoxine 2.0mM was equally effective as L-arginine 10 [sup-4]M alone. 5 Our results confirm that nLDL. dLDL and oxLDL exert inhibitiry effect on endothelium dependent, but not endothelium independent. relaxation of rabbit aorta. ACh and A23187 responses in the presence of any LDL species can be ameliorated by supplementation with L-arginine. L-ascorbate or pyridoxine. either singly or in combination, with no agent or combination proving superior to L-arginine alone. Nevertheless. ACh and A23187 responses are not completely normalised with such supplements, suggesting that there also exists a component of LDL-induced inhibition of endothelium-mediated vasorelaxation that is independent of the nitric oxide system.
- Subjects
VASCULAR endothelium; NITRIC oxide; LOW density lipoproteins; ARGININE; VITAMIN B6; PEOPLE with diabetes; NORADRENALINE; ACETYLCHOLINE; SODIUM nitroferricyanide; VITAMIN therapy; THERAPEUTICS
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 7, p1272
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705545