Division of Reproductive Endocrinology and Infertility, University of Vermont, Burlington, Vermont 05401, USA.
Endocrinology. 2011 Dec;152(12):4927-36. doi: 10.1210/en.2011-1424. Epub 2011 Oct 25.
Clinical research demonstrates an association between polycystic ovary syndrome (PCOS) and endothelial dysfunction, a pathological state widely believed to be a hallmark of vascular disease; the underlying pathways, however, have not been defined. The purpose of this study was to characterize endothelial function in resistance arteries in a novel rat model of PCOS. Female rats were randomized at 3-4 wk to implantation of a 7.5-mg, 90-d dihydrotestosterone (DHT) pellet or a matched placebo. At 15-16 wk, experiments were performed on isolated mesenteric resistance arteries using a pressurized arteriograph. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine (ACh) in the absence and presence of inhibitors for cyclooxygenase (indomethacin) and the thromboxane prostanoid receptor antagonist (SQ29,548). Distensibility was evaluated by measuring vessel diameter from 3-100 mm Hg, and elastin/collagen content was calculated on formalin-fixed vessels. Serum steroid levels were analyzed by sensitive RIA. DHT-induced PCOS rats were heavier, cycled irregularly, and had elevated blood pressure and smaller arterial lumens than controls. Furthermore, DHT vessels showed significantly reduced vasodilatory efficacy to ACh (with no change in sensitivity), reduced distensibility, and increased elastin content compared with controls. Within DHT animals, maximal dilation correlated negatively to DHT levels (r = -0.72) but not to body weight. Preincubation with either indomethacin or SC29,548 abrogated the dysfunction and restored full efficacy to ACh (P < 0.05). This is the first report to demonstrate the presence of endothelial dysfunction in a hyperandrogenic rat model of PCOS and to identify the role of vasoconstrictor prostanoids, allowing for more targeted research regarding the development of disease and potential therapeutic interventions.
临床研究表明多囊卵巢综合征（PCOS）与血管内皮功能障碍之间存在关联，而血管内皮功能障碍被广泛认为是血管疾病的标志之一；然而，其潜在途径尚未明确。本研究旨在描述一种新的多囊卵巢综合征大鼠模型中阻力血管的内皮功能。3-4 周龄的雌性大鼠被随机分为植入 7.5mg、90 天二氢睾酮（DHT）微球或匹配的安慰剂组。15-16 周时，在加压血管描记仪上对分离的肠系膜阻力血管进行实验。通过乙酰胆碱（ACh）对预先收缩的血管的舒张反应来评估内皮功能，同时使用环氧化酶抑制剂（吲哚美辛）和血栓素前列腺素受体拮抗剂（SQ29,548）。通过测量 3-100mmHg 之间的血管直径来评估可扩张性，并通过福尔马林固定血管计算弹力蛋白/胶原蛋白含量。通过灵敏的 RIA 分析血清类固醇水平。DHT 诱导的 PCOS 大鼠比对照组体重更重、不规则循环、血压升高、动脉管腔更小。此外，与对照组相比，DHT 血管对 ACh 的舒张效果明显降低（敏感性无变化）、可扩张性降低、弹力蛋白含量增加。在 DHT 动物中，最大扩张与 DHT 水平呈负相关（r = -0.72），但与体重无关。预先孵育吲哚美辛或 SC29,548 可消除功能障碍并使 ACh 完全恢复效力（P < 0.05）。这是首次报道在多囊卵巢综合征的高雄性激素大鼠模型中存在内皮功能障碍，并确定血管收缩性前列腺素的作用，为疾病的发展和潜在的治疗干预提供了更有针对性的研究。
