Genetic Background and Underlying Mechanism in the Development of Postmenopausal Hypertension

绝经后高血压发生的遗传背景和潜在机制

基本信息

批准号：
07457126
负责人：
SARUTA Takao
金额：
$ 3.33万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

一些流行病学研究表明，更年期后心血管疾病的发生率迅速增加。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。但是，性别差异的潜在机制尚不清楚。绝经后高血压的最重要的临床特征之一是盐敏感性。首先，我们试图通过卵巢抑制DAHL-IWAI-iwai盐敏感性（DS）大鼠建立对绝经后的盐敏感后高血压模型。卵巢切除术加重了DS大鼠的高血压和血小板聚集。雌激素补充剂改善了高血压和血小板功能障碍。收缩压与17beta-雌二醇水平成反比，并与子宫体重与体重比相关。第二，我们研究了卵巢切除术对体内灌注研究的影响。在卵巢切除的DS大鼠中，压力纳他的关系被钝化。三，我们检查了卵巢切除术对细胞内Ca^<2+>的影响。内部CA^<2+>排放能力降低。收缩压与内部Ca^<2+>放电能力成反比。四十五，为了阐明在卵巢切除的DS大鼠中如何增强血小板聚集，我们通过添加蛋白激酶C活化剂或一氧化氧化物合成酶的抑制剂来评估血小板聚集的变化。通过激活蛋白激酶C并抑制一氧化氧化物的合成，通过激活蛋白激酶C来证明血小板聚集在卵巢切除的DS大鼠中得到增强。我们的结论是，卵巢切除术增强了钠诱导的高血压，通过与降低的内部CA^<2+ <2+ <2+ <2+ <2+ <2 e <2 e <2 e <2 e <2+ <2+ <2+ <2 e <2 e <2+ <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2 e <2> <2+ <2> <2 e <2+ <2+ <2+ <2+ DS大鼠中一氧化氮合成。