Perusquía Mercedes, Herrera Nieves, Jasso-Kamel Jaime, González Lorena, Alejandre Nohemí
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, México.
Endocr Res. 2023 Oct 2;48(4):101-111. doi: 10.1080/07435800.2023.2249087. Epub 2023 Aug 20.
Androgens induce vasorelaxation and reduce blood pressure in different mammals, including humans. Most women with polycystic ovary syndrome (PCOS), with hyperandrogenism, are obese and exhibit hypertension; thus, the fact that androgens increase blood pressure (BP) is controversial. Our aim was to determine whether hypertension is produced by androgen excess and/or obesity.
Experiments were performed in dehydroepiandrosterone; (DHEA, s.c)-induced PCOS model. BP from nonobese and obese rats with PCOS (fed a normal or high-fat diet, respectively) was evaluated weekly for 10 weeks by plethysmography and compared between them. We determined whether androgen receptors are responsible for androgen action on BP in rats with PCOS; a group of DHEA-treated rats was implanted with pellets of an antiandrogen and was compared with nonobese rats with PCOS. Isometric tension from aortas of nonobese and obese rats was recorded and compared to explore the integrity of the vascular endothelium when acetylcholine-induced endothelium-dependent vascular relaxation on phenylephrine contraction. Additionally, BP was obtained from 30 women diagnosed with PCOS: nonobese (BMI ≤25) and obese women (BMI ≥35) and compared with healthy counterparts; 15 obese and 15 nonobese women.
Nonobese rats and women with PCOS showed hypotension, while obese rats and women with PCOS displayed hypertension. Healthy obese women were hypertensive and nonobese women remained normotensive. Antiandrogen did not modify the BP values in nonobese rats with PCOS, and obese rats with PCOS revealed marked endothelial dysfunction.
Our findings show that obesity is responsible for hypertension in PCOS and partial endothelial damage was observed, which may contribute to elevated BP. Remarkably, hyperandrogenism is capable of regulating BP to low values that are androgen receptor-independent.
雄激素可诱导不同哺乳动物(包括人类)的血管舒张并降低血压。大多数患有多囊卵巢综合征(PCOS)且雄激素过多的女性肥胖并伴有高血压;因此,雄激素会升高血压这一事实存在争议。我们的目的是确定高血压是否由雄激素过多和/或肥胖引起。
在脱氢表雄酮(DHEA,皮下注射)诱导的PCOS模型中进行实验。通过体积描记法每周评估10周分别喂食正常或高脂饮食的非肥胖和肥胖PCOS大鼠的血压,并对其进行比较。我们确定雄激素受体是否负责PCOS大鼠中雄激素对血压的作用;一组经DHEA处理的大鼠植入抗雄激素丸剂,并与非肥胖PCOS大鼠进行比较。记录非肥胖和肥胖大鼠主动脉的等长张力,并在乙酰胆碱诱导苯肾上腺素收缩时的内皮依赖性血管舒张时比较,以探究血管内皮的完整性。此外,从30名被诊断为PCOS的女性中获取血压:非肥胖(BMI≤25)和肥胖女性(BMI≥35),并与健康对照进行比较;15名肥胖和15名非肥胖女性。
非肥胖大鼠和PCOS女性表现为低血压,而肥胖大鼠和PCOS女性表现为高血压。健康肥胖女性患有高血压,而非肥胖女性血压正常。抗雄激素并未改变非肥胖PCOS大鼠的血压值,且肥胖PCOS大鼠显示出明显的内皮功能障碍。
我们的研究结果表明,肥胖是PCOS高血压发生的原因,并且观察到部分内皮损伤,这可能导致血压升高。值得注意的是,高雄激素血症能够将血压调节至与雄激素受体无关的低值。