Gender differences in atherosclerosis: possible role of nitric oxide.
Gender differences in atherosclerosis: possible role of nitric oxide.
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动脉粥样硬化的性别差异：一氧化氮的可能作用。
DOI：
10.1097/00005344-199511000-00017
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发表时间：
1995
影响因子：
3
通讯作者：
Chaudhuri,G
中科院分区：
文献类型：
--
作者：
Hayashi,T;Fukuto,JM;Ignarro,LJ;Chaudhuri,G
与同龄男性相比，育龄妇女避免患冠心病(CHD)的机制尚不清楚。为了阐明动脉粥样硬化的形成速度是否存在性别差异，我们研究了雄性和雌性兔在饲喂相同的含2%胆固醇的饲料10周和15周后动脉粥样硬化的发展速度。动脉粥样硬化的程度与从这些动物获得的内皮完整的主动脉环基础和刺激释放的一氧化氮(NO)的量有关。在相同的饮食条件下，喂饲高胆固醇饮食(HCD)10周的雌性兔与雄性兔(42%的表面受累)相比，发生的动脉粥样硬化(10%表面受累)非常少。然而，在HCD治疗15周后，没有观察到显著的性别差异。饲喂HCD 10周和15周的动物，其血清胆固醇、高密度脂蛋白和低密度脂蛋白的胆固醇水平相似。对照组主动脉环内皮完整的NO基础释放量显著高于男性。喂饲HCD的雄兔和雌兔的主动脉环内皮依赖性松弛的程度相似，并且这种损害与高脂血症的持续时间有关，而与动脉粥样硬化的程度无关。主动脉环精氨酸含量在男性(257 t52nmol/g湿重)与女性(345 t62nmol/g湿重)之间及对照组与高脂血症组(男性312 t69；女性301 t65nmol/g湿重)之间无显著差异。虽然雌性兔动脉粥样硬化发展速度慢于雄性的确切机制尚不清楚，但雌性兔在喂食高脂饮食前基础NO释放较多，以及其他因素可能参与了这一过程。高脂血症动物内皮依赖性松弛的损害不是由于NO底物精氨酸的可获得性降低。关键词：动脉粥样硬化--主动脉--雌激素--脂类--一氧化氮--性别。与同龄男性相比，育龄女性患冠心病的风险更低(1)。类似地，绝经后妇女的雌激素替代疗法与未接受雌激素替代治疗的绝经后妇女相比，降低了患冠心病的风险。然而，雌激素预防冠心病的确切机制尚不清楚。对兔子(3)和亚人类灵长类动物(4)的研究也表明，雌激素对动脉粥样硬化的发展具有保护作用，而给喂食高胆固醇饮食的兔子服用雌二醇可以降低动脉粥样硬化的发病率。
The mechanism by which women in the reproductive age group are protected from developing coronary heart disease (CHD) as compared with men of similar age is not known. To elucidate whether there is a gender difference in the rate of atherosclerosis formation, we investigated the rate of development of atherosclero-sis in both male and female rabbits fed an identical diet consisting of 2% cholesterol for 10 and 15 weeks. The extent of atherosclerosis was correlated with the amount of basal and stimulated release of nitric oxide (NO) from endothelium-intact aortic rings obtained from these animals. Under identical dietary conditions, the female rabbits fed a high cholesterol diet (HCD) for 10 weeks developed very little atherosclerosis (10% surface involvement) as compared with male rabbits (42% surface involvement). However, no significant gender differences in atherosclerosis were observed after 15 weeks of the HCD. The serum cholesterol, high and low density lipoprotein (HDL and LDL) cholesterol were similar in animals fed the HCD for 10 and 15 weeks. The basal release of NO from endothelium-intact aortic rings was significantly greater in control females as compared with males. The magnitude of endothelium-dependent relaxation of aortic rings obtained from both male and female rabbits fed the HCD were impaired to a similar extent, and this impairment correlated with the duration of hyperlipidemia but not with the extent of atherosclerosis. The arginine content of aortic rings were not different between males (257 t 52 nmol/gwet weight) and females (345 t 62 nmol/g wet weight) or between control and hyperlipidemic groups (males 312 t 69; females 301 t 65 nmol/gwet weight). Although the precise mechanism for the slower rate of development of atherosclerosis in the female rabbits as compared with males is not clear, the greater basal release of NO in females before they were fed a hyperlipidemic diet, as well as other factors, may be involved. The impairment of endothelium-dependent relaxation in hyperlipidemic animals is not due to a decrease in the availability of arginine, the substrate for NO. Key Words: Atherogenesis–Aorta-Estrogens–Lipids–Nitric oxide-Gender.Women in the reproductive age group are at a lower risk for developing coronary heart disease (CHD) as compared with men of similar age (1). Similarly, estrogen replacement therapy in postmenopausal women reduces the risk of CHD relative to the risk in postmenopausal women who do not receive estrogen replacement (2). However, the exact mechanism by which estradiol affords protection against CHD is not known. Studies in rabbits (3) and in subhuman primates (4) also suggest that estrogen affords protection against the development of atherosclerosis and that estradiol administration to rabbits fed a high cholesterol diet led to de-