Some similarities in vascular effects of oleic acid and oxidized low-density lipoproteins on rabbit aorta.
In the present study oxidized low-density lipoproteins (ox-LDL) was prepared by a new simple method: oxidizing LDL by electrolysis-generated free radicals. In endothelium-intact norepinephrine(NE)-precontracted rabbit aortic rings, ox-LDL (2 mg protein/ml)-incubation for 30 min or 3 mM oleic acid for 10 min, significantly attenuated the acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) (both P < 0.01 v control). Such attenuated EDR were sustained after washout. The oleic acid-induced endothelial dysfunction was associated with concomitant reduction of cGMP level in aortic rings. Preincubation of aortic rings with 500 microM L-arginine or 100 u/ml superoxide dismutase for 10 min partly prevented the oleic acid-induced attenuation of EDR and reduction of cGMP, indicating that oleic acid may impair the L-arginine-nitric acid pathway and/or inactivate the nitric oxide. Both ox-LDL and oleic acid potentiated NE-induced aortic ring contraction (both P < 0.01 v control). Such potentiating effects were abolished by preincubation with 1 microM verapamil, indicating the possible involvement of calcium influx in vascular smooth muscle cells during the enhanced contraction. Gas-chromatographic analysis showed that oleic acid content is the highest among all free fatty acids in ox-LDL. In conclusion, we found that oleic acid possesses certain similar vascular effects as ox-LDL in inducing endothelial dysfunction and in enhancing NE-induced vasocontraction in rabbit aortic ring. We proposed that the vasoactive effects of ox-LDL may be resulted partly from the activation or release of active oleic acid molecule during oxidative modification of LDL.
Niu
X L
XL
Department of Pharmacology, Hunan Medical University, Changsha, P.R. of China.
Liu
L Y
LY
Hu
M L
ML
Chen
X
X
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002849:Chromatography, Gas; D006152:Cyclic GMP / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005260:Female; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011817:Rabbits; D017382:Reactive Oxygen Species
D005230:Fatty Acids, Nonesterified; D005609:Free Radicals; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine