Garcia Paz M, Giménez Jose, Bonacasa Barbara, Carbonell Luis F, Miguel Salom G, Quesada Tomas, Hernández Isabel
Department of Physiology, Facultad de Medicina, Universidad de Murcia, Murcia, Spain.
Menopause. 2005 Jul-Aug;12(4):453-9. doi: 10.1097/01.GME.0000151654.10243.01. Epub 2005 Jul 21.
Estrogens may induce cardioprotective effects and prevent neointima formation in response to vascular injury in vivo. The present study evaluated the effect of 17beta-estradiol on myocardial arterial remodeling and on vascular mitogen-activated protein kinase expression in experimental hypertension.
The experiments were performed in intact female spontaneously hypertensive rats (SHR), in SHR that were ovariectomized at 10 or 25 weeks of age, and in ovariectomized SHR that were supplemented with 17 beta-estradiol (OVX + E2, 1.5 mg every 8 weeks, subcutaneous pellets).
At 18 weeks of age, in all myocardial arterioles and small arteries studied, we found significant increases in wall-to-lumen ratio in ovariectomized rats as compared with intact animals. 17beta-estradiol significantly reduced the wall-to-lumen ratio in OVX + E2 rats. Perivascular fibrosis of small coronary arteries was significantly increased by ovariectomy, and this effect was prevented by long-term treatment with 17beta-estradiol. Phosphorylated extracellular signal-regulated kinase 1/2 significantly increased in mesenteric arteries from ovariectomized animals and this effect was prevented by 17beta-estradiol. Wall-to lumen ratio and perivascular fibrosis were significantly higher in older intact animals at 33 weeks of age. However, neither ovariectomy nor estradiol replacement had any effect on long-term hypertension-induced vascular remodeling.
These data suggest that estradiol may exert a beneficial effect by protecting the vasculature from hypertension-induced myocardial arterial remodeling in the early stages of hypertension, but not when chronic alterations are established after a long-term period of hypertension.
雌激素可能具有心脏保护作用,并能预防体内血管损伤后的新生内膜形成。本研究评估了17β-雌二醇对实验性高血压中心肌动脉重塑和血管丝裂原活化蛋白激酶表达的影响。
实验在完整的雌性自发性高血压大鼠(SHR)、10周或25周龄时进行卵巢切除的SHR以及补充17β-雌二醇(OVX + E2,每8周皮下植入1.5 mg)的卵巢切除SHR中进行。
在18周龄时,在所研究的所有心肌小动脉和小动脉中,我们发现与完整动物相比,卵巢切除大鼠的壁腔比显著增加。17β-雌二醇显著降低了OVX + E2大鼠的壁腔比。卵巢切除术显著增加了小冠状动脉的血管周围纤维化,而长期使用17β-雌二醇可预防这种作用。卵巢切除动物肠系膜动脉中磷酸化细胞外信号调节激酶1/2显著增加,而17β-雌二醇可预防这种作用。33周龄的老年完整动物的壁腔比和血管周围纤维化显著更高。然而,卵巢切除术和雌二醇替代对长期高血压诱导的血管重塑均无任何影响。
这些数据表明,雌二醇可能通过在高血压早期保护血管系统免受高血压诱导的心肌动脉重塑而发挥有益作用,但在长期高血压建立慢性改变后则不然。