Effect of atorvastatin on endothelium-dependent constrictor factors in dyslipidemic rabbits

Relaxations to acetylcholine and contractions to acetylcholine in the prese nce of the nitric oxide (NO) synthesis inhibitor (L-N-G- nitroarginine meth yl ester, L-NAME) were studied in aortic rings from rabbits fed either a co ntrol or a diet containing 0.5% cholesterol + 14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg kg(-1) day(-1)). Rings were in cubated with the endothelin (ETA) receptor antagonist BQ123, and/or the thr omboxane A(2) (TXA(2))/prostaglandin H-2 (PGH(2)) receptor antagonist ifetr oban. In rabbits, high cholesterol and triglyceride plasma levels were asso ciated with intimal thickening and blunted acetylcholine-relaxation as comp ared with controls. By contrast, acetylcholine + L-NAME response was higher . Incubation with either ifetroban or BQ123 increased acetylcholine-relaxat ion in both diet groups and it reduced the constrictor response only in dys lipidemic rabbits. Removal of endothelium reduced acetylcholine + L-NAME co ntraction in dyslipidemic rabbits, although increased it in control animals . Atorvastatin treatment reduced plasma lipid levels and lesion size in dys lipidemic animals. Likewise, it prevented acetylcholine-relaxation reductio n. In addition, atorvastatin reduced constrictor response in dyslipidemic r abbits but only in rings with endothelium. Incubation with either ifetroban or BQ123 did not further modify these responses in atorvastatin-treated an imals in any group. These data suggest that ET and TXA(2) availabilities se em to participate in the endothelial dysfunction associated with dyslipidem ia. Atorvastatin treatment reduces intimal thickening and improves endothel ial dysfunction in rabbits. This effect seems to be a consequence of its ab ility to act on ET and TXA(2) systems. (C) 2001 Elsevier Science Inc. Aii r ights reserved.