Rabbit aortic endothelial dysfunction by low-density lipoprotein is attenuated by L-arginine, L-ascorbate and pyridoxine.
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 (50-200 mg protein l-1), or corresponding vehicle, following which they were constricted with noradrenaline 10(-6) M; concentration-relaxation curves were determined to acetylcholine (ACh), A23187, or sodium nitroprusside (NP), in the absence or presence of L-arginine (10(-5)-10(-3) M), L-ascorbate (10(-5)-10(-3) M) and pyridoxine (0.5-2.0 mM). 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, L-ascorbate or pyridoxine each improved ACh and A23187 responses, although none completely normalised endothelium-dependent relaxations. The maximal effect of L-arginine occurred at 10(-4) M. The combination of L-arginine 10(-4) M, L-ascorbate 10(-5) M and pyridoxine 2.0 mM was equally effective as L-arginine 10(-4) M alone. 5. Our results confirm that nLDL, dLDL and oxLDL exert inhibitory effects 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.
Department of Physiology and Pharmacology, Nanjing Medical University, Nanjing, China.
Yong
Y
Ji
Yi
Y
Han
Jianxin
J
Diao
Yan
Y
Huang
Qi
Q
Chen
Albert
A
Ferro
D000328:Adult; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000502:physiology*; D001205:Ascorbic Acid / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000502:physiology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; D001120:Arginine; D011736:Pyridoxine; D001205:Ascorbic Acid