Vagnoni K E, Magness R R
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah 84322, USA.
Biol Reprod. 1998 Oct;59(4):1008-15. doi: 10.1095/biolreprod59.4.1008.
Several enzymes play a role in vasodilation, including cyclooxygenase, which converts arachidonic acid into prostaglandins, and nitric oxide synthase, which converts arginine to citrulline and yields nitric oxide. The effects of endogenous and exogenous estrogen and lipopolysaccharide on uterine artery production of prostacyclin, and levels of cyclooxygenase and nitric oxide synthase were examined. Uterine arteries collected from ewes during the follicular (Day -1 to 0, Day 0 = estrus) or luteal (Day 10) phase were treated in vitro with lipopolysaccharide. In addition, ovariectomized ewes were treated in vivo with estradiol-17beta (5 microg/kg; 120 min) or a vehicle control; arteries from the uteri were treated in vitro with lipopolysaccharide. After 24 h of lipopolysaccharide treatment, culture media were collected for measurement of 6-keto-prostaglandin F1alpha (the stable metabolite of prostacyclin). These uterine arteries were homogenized, and the level of cyclooxygenase and nitric oxide synthase was determined by Western analysis. Lipopolysaccharide stimulated (p < 0.02) prostacyclin production by uterine arteries from both follicular- and luteal-phase sheep although phase of the estrous cycle did not affect prostacyclin responses (p = 0.56) to lipopolysaccharide. In contrast, uterine arteries from ovariectomized sheep treated with estradiol-17beta produced more prostacyclin (p < 0.001) in response to lipopolysaccharide than did uterine arteries from ovariectomized sheep treated with the vehicle control. There was no effect of phase (follicular or luteal) of the estrous cycle on either cyclooxygenase-1 or -2 gene expression. Lipopolysaccharide increased (p = 0.0002) gene expression of cyclooxygenase-2, but not cyclooxygenase-1, in both follicular- and luteal-phase ewes, which was significantly correlated (r2 = 0.91, p = 0.003) with uterine artery production of prostacyclin. Uterine arteries from follicular-phase sheep expressed significantly more nitric oxide synthase-III after lipopolysaccharide exposure than did uterine arteries from luteal-phase ewes (p = 0.03). In contrast, nitric oxide synthase-II was not detected in uterine arteries after lipopolysaccharide exposure. These results suggest that estrogen plays a role in regulating uterine artery responses to lipopolysaccharide.
几种酶在血管舒张中发挥作用，包括将花生四烯酸转化为前列腺素的环氧化酶，以及将精氨酸转化为瓜氨酸并产生一氧化氮的一氧化氮合酶。研究了内源性和外源性雌激素以及脂多糖对子宫动脉前列环素生成、环氧化酶和一氧化氮合酶水平的影响。从处于卵泡期（第 -1 天至第 0 天，第 0 天 = 发情期）或黄体期（第 10 天）的母羊采集子宫动脉，在体外用脂多糖处理。此外，对去卵巢母羊进行体内注射 17β - 雌二醇（5 微克/千克；120 分钟）或载体对照处理；从子宫采集的动脉在体外用脂多糖处理。脂多糖处理 24 小时后，收集培养基用于测量 6 - 酮 - 前列腺素 F1α（前列环素的稳定代谢产物）。将这些子宫动脉匀浆，通过蛋白质印迹分析测定环氧化酶和一氧化氮合酶的水平。脂多糖刺激（p < 0.02）卵泡期和黄体期母羊子宫动脉的前列环素生成，尽管发情周期阶段不影响子宫动脉对脂多糖的前列环素反应（p = 0.56）。相比之下，用 17β - 雌二醇处理的去卵巢母羊的子宫动脉对脂多糖产生的前列环素比用载体对照处理的去卵巢母羊的子宫动脉更多（p < 0.001）。发情周期的阶段（卵泡期或黄体期）对环氧化酶 -1 或 -2 的基因表达均无影响。脂多糖增加（p = 0.0002）卵泡期和黄体期母羊中环氧化酶 -2 的基因表达，但不增加环氧化酶 -1 的基因表达，这与子宫动脉前列环素生成显著相关（r2 = 0.91，p = 0.003）。脂多糖暴露后，卵泡期母羊的子宫动脉比黄体期母羊的子宫动脉表达显著更多的一氧化氮合酶 -III（p = 0.03）。相比之下，脂多糖暴露后子宫动脉中未检测到一氧化氮合酶 -II。这些结果表明雌激素在调节子宫动脉对脂多糖的反应中起作用。
