Department of Physiology and Functional Genomics, University of Florida, P.O. Box 100274, Gainesville, FL 32610, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R433-8. doi: 10.1152/ajpregu.00198.2009. Epub 2009 Dec 2.
It has been suggested that the phosphodiesterase-5 (PDE5) inhibitor sildenafil may be useful in the treatment of hypertension during pregnancy. However, we have reported a selective increase in renal inner medullary PDE5 that participates in the sodium retention of pregnancy. Therefore, the purpose of this study was to determine whether oral sildenafil treatment impairs maternal plasma volume expansion and/or fetal growth during rat pregnancy. Rats received sildenafil (10 mg x kg(-1) x day(-1), 50 mg x kg(-1) x day(-1), or 90 mg x kg(-1) x day(-1)) or vehicle on days 4-20 of pregnancy. On days 14-19, rats were housed in metabolic cages for collection of urine and measurement of food and water intake. Terminal hemodynamic and fetal measurements were taken on day 20. None of the sildenafil doses lowered blood pressure, and although all doses increased plasma cGMP concentrations, only the highest dose increased aortic and inner medullary cGMP content. Sildenafil had no effect on maternal weight gain; however, the highest dose decreased both plasma volume and renal sodium retention. The pup number and size were similar among the groups. Therefore, these studies suggest that low doses of systemic sildenafil may be safe during pregnancy in the rat, but higher doses may interfere with the physiological sodium retention and volume expansion of pregnancy. The effects of systemic sildenafil on blood pressure and sodium retention during hypertension in human pregnancy remain to be examined.
有人提出，磷酸二酯酶-5（PDE5）抑制剂西地那非可能对治疗妊娠高血压有用。然而，我们已经报道了肾髓质 PDE5 的选择性增加，它参与了妊娠期间的钠潴留。因此，本研究旨在确定口服西地那非治疗是否会损害妊娠大鼠母体血浆容量扩张和/或胎儿生长。大鼠在妊娠第 4-20 天接受西地那非（10mg/kg/天、50mg/kg/天或 90mg/kg/天）或载体治疗。在第 14-19 天，大鼠被安置在代谢笼中以收集尿液并测量食物和水的摄入量。在第 20 天进行终末血液动力学和胎儿测量。西地那非的任何剂量都没有降低血压，尽管所有剂量都增加了血浆 cGMP 浓度，但只有最高剂量增加了主动脉和内髓质 cGMP 含量。西地那非对母体体重增加没有影响；然而，最高剂量降低了血浆容量和肾钠潴留。各组之间的幼仔数量和大小相似。因此，这些研究表明，在妊娠大鼠中，低剂量的全身西地那非可能是安全的，但高剂量可能会干扰妊娠期间的生理钠潴留和容量扩张。全身西地那非对人类妊娠高血压期间血压和钠潴留的影响仍有待研究。
