Genetic Background and Underlying Mechanism in the Development of Postmenopausal Hypertension

几项流行病学研究表明，绝经后心血管疾病的发病率迅速增加。高血压是心血管疾病的主要危险因素之一，其患病率存在性别差异。然而，性别差异的潜在机制仍不清楚。绝经后高血压最重要的临床特征之一是盐敏感性。首先，我们试图通过切除卵巢的Dahl-Iwai盐敏感（DS）大鼠建立雌性盐敏感绝经后高血压模型。卵巢切除术加重DS大鼠高血压和血小板聚集。补充雌激素可改善高血压和血小板功能障碍。收缩压与17 -雌二醇水平和子宫重量与体重比呈负相关。其次，我们通过体内灌注研究卵巢切除术对压力钠尿的影响。去卵巢大鼠血压-尿钠关系减弱。第三，我们研究了卵巢切除术对细胞内Ca^<2+>的影响。内部Ca^<2+>放电容量降低。收缩压与内部Ca^<2+>放电能力呈负相关。第四，为了阐明在去卵巢的DS大鼠中血小板聚集是如何增强的，我们通过添加蛋白激酶C激活剂或一氧化氮合酶抑制剂来评估血小板聚集的变化。在去卵巢的DS大鼠中，通过激活蛋白激酶C和抑制一氧化氮合成，血小板聚集被证明是增强的。我们得出结论，卵巢切除术通过减弱压力-钠尿关系来增强钠诱导的高血压，这与DS大鼠体内Ca^<2+>放电能力降低和血小板聚集增加有关，这是通过激活蛋白激酶C和抑制一氧化氮合成来实现的。

Several epidemiological studies have shown that the incidence of cardiovascular disease rapidly increases after menopause. Hypertension is one of the main risk factors for cardiovascular disease, and there are gender differences in its prevalence. However, underlying mechanisms of sexual differences remain unclear. One of the most important clinical characteristics of postmenopausal hypertension is salt sensitivity.First, we attempted to establish a female salt-sensitive postmenopausal hypertensive model by ovariectomizing Dahl-Iwai salt-sensitive (DS) rats. Ovariectomy aggravated hypertension and platelet aggregation in DS rats. Estrogen supplement improved hypertension and platelet dysfunction. Systolic blood pressure was inversely correlated with 17beta-estradiol level and with uterus weight to body weight ratio.Second, we investigated the effect of ovariectomy on pressure-natriuresis by in vivo perfusion studies. The pressure-natriuresis relationship was blunted in ovariectomized DS rats.Third, we examined the effect of ovariectomy on intracellular Ca^<2+>. The internal Ca^<2+> discharge capacity was reduced. Systolic blood pressure was inversely correlated with the internal Ca^<2+> discharge capacity.Fourth, to clarify how platelet aggregation was enhanced in ovariectomized DS rats, we assessed the changes in platelet aggregation by adding a protein kinase C activator or an inhibitor of nitric oxide synthase. Platelet aggregation was proved to be augmented in ovariectomized DS rats by activating protein kinase C and by suppressing nitric oxide synthesis.We concluded that ovariectomy enhanced sodium-induced hypertension by blunting the pressure-natriuresis relationship, associated with the decreased internal Ca^<2+> discharge capacity and increased platelet aggregation through protein kinase C activation and the suppression of nitric oxide synthesis in DS rats.