Effect of pravastatin on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine in rat aorta

• 来源期刊: 中国药理学报（英文版）
• 关键词: pravastatin lysophosphatidylcholine vascularendothelium vasodilation superoxidedismutase L-arginine nitric oxide thoracicaorta rats
• 年，卷（期）: 2005,（1）
• 页码范围: 92-98
• 页数: 7页
• 语种: 英文

摘要

Aim: To investigate the effects of pravastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on impaired endothelium-dependent relaxation induced by lysophosphatidylcholine (LPC), the major component of oxidized low-density lipoprotein, in rat thoracic aorta. Methods: Both the endothelium-dependent relaxation response to acetylcholine and the endotheliumindependent relaxation response to sodium nitroprusside of aortic rings were measured by recording isometric tension after the rings were exposed to LPC in the absence or presence of pravastatin to estimate the injury effect of LPC and the protective effect of pravastatin on the aortic endothelium, respectively. Results:Exposure of aortic rings to LPC (1-10 μrmol/L) for 30 min induced a significant concentration-dependent inhibition of endothelium-dependent relaxation to acetylcholine, but did not affect endothelium-independent relaxation in response to sodium nitroprusside. Pre-incubation of aortic rings with pravastatin (0.3-3mmol/L) for 15 min and then co-incubation of the rings with LPC (3 μrmol/L) for another 30 min significantly attenuated the inhibition of endothelium-dependent relaxation induced by LPC. This protective effect of pravastatin (1 mmol/L) was abolished by NG-nitro-L-arginine methyl ester (30 μmol/L), an inhibitor of nitric oxide synthase, but not by indomethacin (10 μmol/L), an inhibitor of cyclooxygenase. Moreover, protein kinase C inhibitor chelerythrine (1μmol/L) the superoxide anion scavenger superoxide dismutase (200 kU/L), and the nitric oxide precursor L-arginine (3 mmol/L) also improved the impaired endotheliumdependent relaxation induced by LPC, similar to the effects of pravastatin.Conclusion: Pravastatin can protect the endothelium against functional injury induced by LPC in rat aorta, a fact which is related to increasing nitric oxide bioavailability.