Dowell F J, Hamilton C A, Reid J L
Department of Medicine and Therapeutics, University of Glasgow, Scotland.
J Cardiovasc Pharmacol. 1996 Feb;27(2):235-9. doi: 10.1097/00005344-199602000-00009.
Animal studies, while generally showing loss of endothelium-dependent responses after an elevation in plasma cholesterol, have provided conflicting reports with regard to recovery of function after normalisation of cholesterol level. Therefore, we assessed changes in vascular function after a period of hypercholesterolaemia and the subsequent effect of normalisation of cholesterol levels. Contractile responses to phenylephrine (PE) and endothelium-dependent relaxation in response to carbachol were examined in thoracic aorta from New Zealand White rabbits (NZW) fed a 0.3% cholesterol diet for 20 weeks, from NZW fed a 0.3% cholesterol diet for 20 weeks, followed by standard diet for 20 more weeks, and from their respective age-matched controls. Cholesterol levels were increased in rabbits receiving the 0.3% cholesterol diet (12.7 +/- 3.2 mM; 0.5 +/- 0.1 mM control) and returned to normal when standard diet was reintroduced (0.8 +/- 2.0 mM). Contractile responses were not affected by the period of hypercholesterolaemia. Carbachol-induced relaxation of a submaximal PE contraction was impaired after the period of hypercholesterolaemia (Emax 69 +/- 9%; 95 +/- 3% age-matched (control); the effect was reversed after reintroduction of standard diet (Emax 79 +/- 6%; 82 +/- 2% age-matched control). Our results demonstrate that endothelium-dependent relaxation is impaired after a long-term 0.3% cholesterol diet. Furthermore, after reintroduction of a normal diet, there is no further impairment of endothelium-dependent relaxation and endothelium function improves.
动物研究虽然总体上显示血浆胆固醇升高后内皮依赖性反应丧失，但关于胆固醇水平恢复正常后功能恢复的报道却相互矛盾。因此，我们评估了高胆固醇血症一段时间后的血管功能变化以及胆固醇水平恢复正常后的后续影响。检测了给予0.3%胆固醇饮食20周的新西兰白兔（NZW）、给予0.3%胆固醇饮食20周后再给予标准饮食20周的NZW以及各自年龄匹配的对照组的胸主动脉对去氧肾上腺素（PE）的收缩反应和对卡巴胆碱的内皮依赖性舒张反应。接受0.3%胆固醇饮食的兔子胆固醇水平升高（12.7±3.2 mM；对照组为0.5±0.1 mM），重新引入标准饮食后恢复正常（0.8±2.0 mM）。收缩反应不受高胆固醇血症时期的影响。高胆固醇血症时期后，卡巴胆碱诱导的次最大PE收缩舒张受损（最大效应Emax为69±9%；年龄匹配对照组为95±3%）；重新引入标准饮食后这种效应得到逆转（Emax为79±6%；年龄匹配对照组为82±2%）。我们的结果表明，长期给予0.3%胆固醇饮食后内皮依赖性舒张受损。此外，重新引入正常饮食后，内皮依赖性舒张没有进一步受损，内皮功能得到改善。
