Department of Cell and Molecular Biology.
Women's Health Research Center.
J Hypertens. 2022 Apr 1;40(4):712-722. doi: 10.1097/HJH.0000000000003067.
Polycystic ovary syndrome (PCOS) is characterized by reproductive and metabolic dysfunction, and elevated blood pressure (BP). The cardiometabolic consequences of maternal hyperandrogenemia on offspring, either as adults or with aging, have not been well studied. We previously found that male offspring of hyperandrogenemic female (HAF) rats, a model of PCOS, are normotensive but have an exaggerated pressor response to angiotensin (Ang) II.
In this study, the hypothesis was tested that adult and aging female offspring of HAF rats develop a metabolic and hypertensive phenotype. Control and HAF rats were implanted prepubertally with placebo or dihydrotestosterone pellets, which continued throughout pregnancy and lactation.
Female offspring of HAF dams had lower birth weight than female control offspring. Although female HAF offspring (aged 16-24 weeks) had no differences in intrarenal Ang II, plasma lipids or proteinuria, they did have lower intrarenal Ang (1-7) and lower nitrate/nitrite excretion than controls. Adult HAF offspring had similar baseline BP as controls, but had an attenuated pressor response to Ang II. With aging (16-20 months), female HAF offspring remained normotensive with an attenuated pressor response to Ang II and high salt diet but more proteinuria and higher intrarenal Ang(1-7) than controls.
Taken together, these data suggest that female HAF offspring are protected from developing hypertension, but may be at risk for renal injury with aging. Future studies are necessary to determine whether adult and postmenopausal offspring of PCOS women are at increased risk for cardiovascular dysfunction.Graphical abstract:http://links.lww.com/HJH/B820.
多囊卵巢综合征（PCOS）的特征是生殖和代谢功能障碍以及血压升高。母体高雄激素血症对子代的心脏代谢后果，无论是在成年期还是随着年龄的增长，尚未得到很好的研究。我们之前发现，高雄激素血症雌性（HAF）大鼠的雄性后代血压正常，但对血管紧张素（Ang）II 的加压反应增强，这是 PCOS 的一种模型。
本研究检验了这样一个假设，即 HAF 大鼠的成年和老年雌性后代会出现代谢和高血压表型。对照和 HAF 大鼠在青春期前植入安慰剂或双氢睾酮丸，这些药丸在整个孕期和哺乳期都持续存在。
HAF 母鼠的雌性后代出生体重低于对照雌性后代。尽管 HAF 母鼠的雌性后代（16-24 周龄）的肾内 Ang II、血浆脂质或蛋白尿没有差异，但它们的肾内 Ang（1-7）和硝酸盐/亚硝酸盐排泄量低于对照组。成年 HAF 后代的基础血压与对照组相似，但对 Ang II 的升压反应减弱。随着年龄的增长（16-20 个月），HAF 雌性后代仍然保持血压正常，对 Ang II 和高盐饮食的升压反应减弱，但蛋白尿和肾内 Ang（1-7）水平高于对照组。
综上所述，这些数据表明，HAF 雌性后代免受高血压的发展，但随着年龄的增长，可能有肾脏损伤的风险。未来的研究需要确定 PCOS 女性的成年和绝经后后代是否有更高的心血管功能障碍风险。
