Vera Rocio, Jiménez Rosario, Lodi Federica, Sánchez Manuel, Galisteo Milagros, Zarzuelo Antonio, Pérez-Vizcaíno Francisco, Duarte Juan
Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.
Menopause. 2007 Sep-Oct;14(5):933-40. doi: 10.1097/GME.0b013e31802d9785.
The soy-derived phytoestrogen genistein improves endothelial function in postmenopausal women and ovariectomized (OVX) normotensive rats. We hypothesized that genistein would improve vascular reactivity involving changes in endothelial nitric oxide synthase (NOS) expression and its regulatory proteins (caveolin and calmodulin), angiotensin II receptor, and/or oxidative status in OVX spontaneously hypertensive rats (SHRs).
After ovariectomy or sham operation, 23-week-old female SHRs received either 17beta-estradiol (2 mg/kg/wk SC), genistein (10 mg/kg/d by gavage), or placebo.
In OVX rats, final body weight was increased and uterus weight was decreased, and these values were reduced and increased, respectively, by 17beta-estradiol but unaffected by genistein. Acetylcholine-induced endothelium-dependent vasorelaxation was significantly blunted in aortas from OVX placebo SHRs. The contractions induced by the NOS inhibitor L-NAME and angiotensin II in OVX placebo were lower and higher, respectively, than in sham rats. Estradiol and genistein restored these functional changes. Aortic endothelial NOS and calmodulin-1 expression were unchanged, whereas caveolin-1 and angiotensin II receptor expression was increased in OVX rats. Estradiol and genistein treatment did not modify endothelial NOS, but normalized caveolin-1 and angiotensin II receptor and increased calmodulin-1 expression. Vascular superoxide production was increased in OVX placebo and normalized by both estradiol and genistein.
Genistein prevented all cardiovascular changes induced by estrogen depletion in SHRs to a similar extent as estradiol but had no uterotrophic effect. The present findings may help to explain the potential benefits of genistein as a therapeutic agent for preventing menopausal vascular complications, especially in hypertensive women.
大豆衍生的植物雌激素染料木黄酮可改善绝经后女性和去卵巢（OVX）正常血压大鼠的内皮功能。我们假设染料木黄酮可改善血管反应性，这涉及OVX自发性高血压大鼠（SHR）中内皮型一氧化氮合酶（NOS）表达及其调节蛋白（小窝蛋白和钙调蛋白）、血管紧张素II受体和/或氧化状态的变化。
在进行卵巢切除或假手术后，23周龄的雌性SHR接受17β-雌二醇（2mg/kg/周，皮下注射）、染料木黄酮（10mg/kg/天，灌胃）或安慰剂。
在OVX大鼠中，最终体重增加，子宫重量减少，17β-雌二醇分别使这些值降低和增加，但染料木黄酮对其无影响。乙酰胆碱诱导的内皮依赖性血管舒张在OVX安慰剂SHR的主动脉中明显减弱。NOS抑制剂L-NAME和血管紧张素II在OVX安慰剂中诱导的收缩分别低于和高于假手术大鼠。雌二醇和染料木黄酮恢复了这些功能变化。主动脉内皮型NOS和钙调蛋白-1表达未改变，而OVX大鼠中小窝蛋白-1和血管紧张素II受体表达增加。雌二醇和染料木黄酮治疗未改变内皮型NOS，但使小窝蛋白-1和血管紧张素II受体正常化并增加了钙调蛋白-1表达。OVX安慰剂中血管超氧化物生成增加，雌二醇和染料木黄酮均可使其正常化。
染料木黄酮在SHR中预防雌激素缺乏引起的所有心血管变化的程度与雌二醇相似，但无促子宫生长作用。本研究结果可能有助于解释染料木黄酮作为预防绝经后血管并发症，尤其是高血压女性血管并发症的治疗药物的潜在益处。
