Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912-2300, United States.
Steroids. 2011 Sep-Oct;76(10-11):991-7. doi: 10.1016/j.steroids.2011.03.011. Epub 2011 Mar 31.
Few studies have examined the potential effects of childbirth on the responses of the female vasculature--especially the resistance microvasculature of non-reproductive tissues. In the present study we have investigated the response of mesenteric microvascular resistance vessels to estrogen (E2), an important vasoactive hormone. Vessels were obtained from either nulliparous or postpartum female Sprague-Dawley rats, and isometric tension studies were performed. We found that E2 induced a concentration-dependent, endothelium-independent relaxation of microvessels precontracted with 10(-5) M phenylephrine; however, E2-induced relaxation was reduced by nearly half in vessels from postpartum animals compared to nulliparous controls. Inhibiting nitric oxide synthase activity with 10(-4) M L-NMMA or L-NPA (which exhibits selectivity for type 1 or nNOS) attenuated the relaxation effect of E2 on arteries from nulliparous animals. In contrast, L-NPA had little effect on arteries from postpartum animals, suggesting a reduced influence of nNOS after parturition. Moreover, expression of nNOS protein in microvessels was decreased 39% in the postpartum state compared to arteries from nulliparous animals. We propose that the impaired E2-induced relaxation response of microvessels from postpartum animals reflects a downregulation of NO production due to lower nNOS expressed in vascular smooth muscle cells. We measured a 73% decrease in serum E2 levels in the postpartum state compared to nulliparous animals. Because E2 has been shown to increase nNOS protein expression, we propose that lower E2 levels after parturition decrease expression of nNOS, leading to a reduced vasodilatory capacity of resistance microvessels.
很少有研究探讨分娩对女性血管系统反应的潜在影响——尤其是非生殖组织的阻力微血管。在本研究中，我们研究了雌激素（E2）对肠系膜微血管阻力血管的反应，E2 是一种重要的血管活性激素。血管取自未生育或产后的雌性 Sprague-Dawley 大鼠，并进行等长张力研究。我们发现，E2 诱导浓度依赖性、内皮非依赖性的 10(-5) M 苯肾上腺素预收缩微血管松弛；然而，与未生育对照组相比，产后动物的血管中 E2 诱导的松弛作用减少了近一半。用 10(-4) M L-NMMA 或 L-NPA（对 1 型或 nNOS 具有选择性）抑制一氧化氮合酶活性，减弱了 E2 对未生育动物动脉的松弛作用。相比之下，L-NPA 对产后动物的动脉几乎没有影响，这表明分娩后 nNOS 的影响降低。此外，与未生育动物的动脉相比，产后动物的微血管中 nNOS 蛋白的表达降低了 39%。我们提出，产后动物微血管中 E2 诱导的松弛反应受损反映了由于血管平滑肌细胞中 nNOS 表达降低导致的 NO 生成下调。我们测量到产后状态下血清 E2 水平比未生育动物降低了 73%。由于 E2 已被证明可增加 nNOS 蛋白表达，我们提出产后 E2 水平降低会降低 nNOS 的表达，从而导致阻力微血管的血管扩张能力降低。
