Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Ehime, Japan.
Thromb Res. 2010 Dec;126(6):504-10. doi: 10.1016/j.thromres.2010.09.013.
Menopause is associated with marked changes in the endocrine profile, and increases the risk of vascular disease. However, the effect of hormones on the vascular system is still unclear. Therefore, the aim of this study was to examine the effects of endocrine status in female rats on nitric oxide (NO) production, inflammatory reactions and thrombus organization potency in the mesenteric microcirculation.
Female Wistar rats were divided into four groups: proestrus, metestrus, ovariectomized (OVX) and OVX plus estradiol treatment (OVX+E2). NO was imaged using an NO-sensitive dye. The leukocyte and platelet velocities relative to the erythrocyte velocity (VW/VRC and VP/VRE, respectively) and thrombi sizes created by laser radiation were measured as thrombogenesis indices.
Changes in endocrine status did not affect vascular function in the arterioles. However, in venules, NO production, VW/VRC and VP/VRE were decreased in the OVX group compared with the proestrus and metestrus states. Thrombus size was significantly greater in the OVX group than in the proestrus and metestrus states. Administration of E2 for 2 weeks restored NO production, VW/VRC and VP/VRE to control levels.
Changes in endocrine status did not affect arterioles. In contrast, in venules, reduced estrogen levels led to a decrease in NO production, thereby increasing thrombogenesis. Estrogen replacement restored NO production and leukocyte and platelet velocities, reducing thrombus formation relative to OVX. Although it is unclear how E2 reduces thrombus formation, our results indicate that leukocyte and platelet adhesion to the endothelium is a target for E2 via NO.
绝经与内分泌谱的显著变化有关,并增加了血管疾病的风险。然而,激素对血管系统的影响仍不清楚。因此,本研究旨在研究雌性大鼠内分泌状态对肠系膜微循环中一氧化氮(NO)产生、炎症反应和血栓组织形成能力的影响。
将雌性 Wistar 大鼠分为 4 组:发情前期、发情期、卵巢切除(OVX)和卵巢切除加雌激素治疗(OVX+E2)。使用 NO 敏感染料对 NO 进行成像。白细胞和血小板相对于红细胞的速度(VW/VRC 和 VP/VRE)和激光辐射引起的血栓大小被测量为血栓形成指数。
内分泌状态的变化并不影响小动脉的血管功能。然而,在小静脉中,与发情前期和发情期相比,OVX 组的 NO 产生、VW/VRC 和 VP/VRE 降低。与发情前期和发情期相比,OVX 组的血栓大小显著增加。用 E2 治疗 2 周可将 NO 产生、VW/VRC 和 VP/VRE 恢复到对照水平。
内分泌状态的变化不影响小动脉。相比之下,在小静脉中,雌激素水平降低导致 NO 产生减少,从而增加血栓形成。雌激素替代可恢复 NO 产生和白细胞及血小板速度,相对于 OVX 减少血栓形成。虽然尚不清楚 E2 如何减少血栓形成,但我们的结果表明,白细胞和血小板与内皮的粘附是 E2 通过 NO 的作用靶点。