Vagnoni K E, Shaw C E, Phernetton T M, Meglin B M, Bird I M, Magness R R
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53715, USA.
Am J Physiol. 1998 Nov;275(5):H1845-56. doi: 10.1152/ajpheart.1998.275.5.H1845.
During the follicular phase of the ovarian cycle, when the local estrogen-to-progesterone ratio is elevated, uterine blood flow is elevated. This vasodilatory response is reproduced by exogenous 17beta-estradiol (E2beta) administration via a nitric oxide (NO)-mediated mechanism. We hypothesized that endogenous ovarian estrogen and exogenous E2beta treatment elevate expression of endothelial cell-derived NO synthase (eNOS) in uterine, but not in systemic, arteries. Uterine, mammary, and systemic (renal and/or omental) arteries were collected from 1) ewes synchronized to the follicular (day -1 to day 0) or luteal (day 10) phases of the ovarian cycle (n = 4 per phase), 2) ovariectomized ewes 120 min after systemic vehicle or E2beta (5 micrograms/kg iv) treatment, and 3) ovariectomized ewes on days 0, 3, 6, 8, and 10 of E2beta (5 micrograms/kg iv, followed by 6 micrograms/kg per day) treatment. Expression of eNOS was localized primarily to the endothelium rather than vascular smooth muscle (VSM) in all arteries examined by immunohistochemistry and Western analysis; inducible NOS was not detected in either endothelium or VSM. Expression of eNOS protein was greater (P < 0.05) in uterine, but not in systemic, artery endothelium-isolated protein collected from follicular versus luteal phase ewes. Acute systemic E2beta treatment of ovariectomized ewes increased (P < 0.05) eNOS protein levels in uterine artery endothelium. Prolonged E2beta administration progressively increased uterine, but not systemic, artery endothelial eNOS protein expression. Therefore, the increased local estrogen-to-progesterone ratio during the follicular phase locally elevates eNOS expression, which possibly elevates uterine blood flow. These responses can be partly reproduced with E2beta administration.
在卵巢周期的卵泡期，当局部雌激素与孕酮的比值升高时，子宫血流量会增加。这种血管舒张反应可通过外源性给予17β-雌二醇（E2β），经由一氧化氮（NO）介导的机制重现。我们推测，内源性卵巢雌激素和外源性E2β治疗可提高子宫动脉而非全身动脉中内皮细胞源性一氧化氮合酶（eNOS）的表达。从以下几组羊中采集子宫、乳腺和全身（肾和/或网膜）动脉：1）处于卵巢周期卵泡期（第-1天至第0天）或黄体期（第10天）的母羊（每个阶段n = 4）；2）在全身给予溶剂或E2β（5微克/千克静脉注射）治疗120分钟后的去卵巢母羊；3）在E2β（5微克/千克静脉注射，随后每天6微克/千克）治疗的第0、3、6、8和10天的去卵巢母羊。通过免疫组织化学和蛋白质印迹分析检测发现，在所有检测的动脉中，eNOS的表达主要定位于内皮细胞而非血管平滑肌（VSM）；在内皮细胞或VSM中均未检测到诱导型NOS。从卵泡期与黄体期母羊分离的子宫动脉内皮蛋白中，eNOS蛋白的表达更高（P < 0.05），但在全身动脉中并非如此。对去卵巢母羊进行急性全身E2β治疗可增加（P < 0.05）子宫动脉内皮中的eNOS蛋白水平。长期给予E2β可逐渐增加子宫动脉而非全身动脉内皮中的eNOS蛋白表达。因此，卵泡期局部雌激素与孕酮比值的增加会局部提高eNOS的表达，这可能会增加子宫血流量。这些反应可通过给予E2β部分重现。
