Bolego C, Cignarella A, Ruzza R, Zaarour C, Messi E, Zanisi M, Puglisi L
Institute of Pharmacological Sciences, University of Milan, Italy.
Life Sci. 1997;60(25):2291-302. doi: 10.1016/s0024-3205(97)00284-1.
In an attempt to study the mechanisms by which estrogens affect vascular responses, we utilized aortic preparations from intact and ovariectomized female rats receiving low- and high-dose subcutaneous estrogen treatments. Oil-treated, as well as male rats, served as controls. In ovariectomized females, low-dose 17-beta-estradiol injections (5 microg/kg daily for two days) affected the basal release of nitric oxide, as evaluated by concentration-related curves to superoxide dismutase and N(G)-Methyl-L-arginine acetate, which was found to be greater in 17-beta-estradiol-treated females compared to oil-treated females or males. Conversely, the nitric oxide-related vascular relaxation evoked by acetylcholine and sodium nitroprusside was unchanged. Prostacyclin production was also evaluated. Aortic rings from ovariectomized 17-beta-estradiol-treated females released significantly more prostacyclin than those from oil-treated females. These results point out a possible role for nitric oxide and prostacyclin in the vascular protection brought about by physiological levels of estrogens. When intact females were treated with high doses of ethynilestradiol (100 microg/Kg daily for one month), a component of contraceptive pills, either the basal release of nitric oxide, or acetylcholine-induced relaxation underwent a significant decrease. Likewise, the relaxant responses to sodium nitroprusside were impaired in the aortic rings obtained from ethynilestradiol-treated animals when compared to controls. Similarly, the amount of prostacyclin released from aortic tissues obtained from ethynilestradiol-treated animals was significantly reduced. These results may provide a possible explanation for the higher incidence of cardiovascular disease in women who take contraceptive preparations containing high doses of estrogens.
为了研究雌激素影响血管反应的机制，我们使用了来自完整雌性大鼠和去卵巢雌性大鼠的主动脉制剂，这些大鼠接受了低剂量和高剂量的皮下雌激素治疗。用油处理的大鼠以及雄性大鼠作为对照。在去卵巢雌性大鼠中，低剂量17-β-雌二醇注射（每天5微克/千克，共两天）影响一氧化氮的基础释放，通过超氧化物歧化酶和N（G）-甲基-L-精氨酸醋酸盐的浓度相关曲线评估，发现与用油处理的雌性大鼠或雄性大鼠相比，17-β-雌二醇处理的雌性大鼠中一氧化氮的基础释放量更大。相反，乙酰胆碱和硝普钠引起的与一氧化氮相关的血管舒张没有变化。还评估了前列环素的产生。去卵巢的17-β-雌二醇处理的雌性大鼠的主动脉环释放的前列环素明显多于用油处理的雌性大鼠。这些结果指出了一氧化氮和前列环素在雌激素生理水平带来的血管保护中的可能作用。当完整雌性大鼠用高剂量乙炔雌二醇（每天100微克/千克，共一个月）治疗时，乙炔雌二醇是避孕药的一种成分，一氧化氮的基础释放或乙酰胆碱诱导的舒张均显著降低。同样，与对照组相比，从乙炔雌二醇处理的动物获得的主动脉环对硝普钠的舒张反应受损。类似地，从乙炔雌二醇处理的动物获得的主动脉组织释放的前列环素量也显著减少。这些结果可能为服用含高剂量雌激素避孕药的女性心血管疾病发病率较高提供一个可能的解释。
