Novak J, Danielson L A, Kerchner L J, Sherwood O D, Ramirez R J, Moalli P A, Conrad K P
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, and Magee-Women's Research Institute, Pittsburgh, Pennsylvania, USA.
J Clin Invest. 2001 Jun;107(11):1469-75. doi: 10.1172/JCI11975.
Marked vasodilation in the kidney and other nonreproductive organs is one of the earliest maternal adaptations to occur during pregnancy. Despite the recognition of this extraordinary physiology for over four decades, the gestational hormone responsible has remained elusive. Here we demonstrate a key role for relaxin, a member of the IGF family that is secreted by the corpus luteum in humans and rodents. Using a gravid rodent model, we employ two approaches to eliminate relaxin or its biological activity from the circulation: ovariectomy and administration of neutralizing antibodies. Both abrogate the gestational elevation in renal perfusion and glomerular filtration, as well as preventing the reduction in myogenic reactivity of isolated, small renal arteries. Osmoregulatory changes, another pregnancy adaptation, are also abolished. Our results indicate that relaxin mediates the renal vasodilatory responses to pregnancy and thus may be important for maternal and fetal health. They also raise the likelihood of a role for relaxin in other cardiovascular changes of pregnancy, and they suggest that, like estrogen, relaxin should be considered a regulator of cardiovascular function.
肾脏和其他非生殖器官的显著血管舒张是孕期最早出现的母体适应性变化之一。尽管四十多年来人们已认识到这种非凡的生理现象,但起作用的妊娠激素一直难以确定。在此,我们证明了松弛素的关键作用,松弛素是胰岛素样生长因子(IGF)家族的一员,在人类和啮齿动物中由黄体分泌。利用妊娠啮齿动物模型,我们采用两种方法从循环中消除松弛素或其生物活性:卵巢切除术和注射中和抗体。这两种方法都消除了孕期肾脏灌注和肾小球滤过的升高,同时也阻止了孤立的小肾动脉肌源性反应性的降低。另一种孕期适应性变化——渗透调节变化也被消除。我们的结果表明,松弛素介导了孕期的肾血管舒张反应,因此可能对母体和胎儿健康至关重要。这些结果还增加了松弛素在孕期其他心血管变化中发挥作用的可能性,并且表明,与雌激素一样,松弛素应被视为心血管功能的调节因子。