Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA.
Exp Biol Med (Maywood). 2021 Jul;246(13):1554-1562. doi: 10.1177/15353702211003294. Epub 2021 Apr 1.
Prenatal dexamethasone has been shown to increase blood pressure in male offspring but the mechanism for the increase in blood pressure is unclear. The present study examined if prenatal programming by maternal injection of dexamethasone on days 15 and 16 of gestation affected the blood pressure comparably in female and male offspring. Our hypothesis was that males would be affected by prenatal dexamethasone to a greater extent than females and that either an increase in renal tubular transporter abundance or an increase in renin or aldosterone system would be associated with hypertension with prenatal programming. Prenatal dexamethasone increased blood pressure at two months and six months of age and resulted in proteinuria and albuminuria at six months in male but not female rat offspring. There was no effect of prenatal dexamethasone on blood pressure and proteinuria at one month in male and in female offspring. While prenatal dexamethasone increased male renal thick ascending limb sodium potassium two chloride cotransporter protein abundance at two months, prenatal dexamethasone on days 15 and 16 of gestation did not affect transporter abundance in males at other ages, nor did it affect proximal tubule sodium/hydrogen exchanger or distal convoluted tubule sodium chloride cotransporter protein abundance at any age. There was no difference in systemic renin or aldosterone in the prenatal dexamethasone group compared to same sex controls. In conclusion, male but not female offspring have an increase in blood pressure and urinary protein excretion with prenatal dexamethasone. The increase in blood pressure with prenatal programming was not associated with a consistent increase in renal tubular transporter protein abundance, nor plasma renin activity and serum aldosterone.
产前地塞米松已被证明可使雄性后代的血压升高，但血压升高的机制尚不清楚。本研究检查了母体在妊娠第 15 和 16 天注射地塞米松是否会以类似的方式影响雌性和雄性后代的血压。我们的假设是，雄性受产前地塞米松的影响比雌性更大，并且肾管状转运蛋白的丰度增加或肾素或醛固酮系统的增加与产前编程引起的高血压有关。产前地塞米松可使雄性仔鼠在两个月和六个月大时的血压升高，并导致其在六个月大时出现蛋白尿和白蛋白尿，但对雌性仔鼠无此影响。产前地塞米松在一个月时对雄性和雌性仔鼠的血压和蛋白尿均无影响。虽然产前地塞米松可使雄性肾髓质升支粗段钠钾 2 氯共转运蛋白的蛋白丰度在两个月大时增加，但在妊娠第 15 和 16 天给予地塞米松不会影响雄性在其他年龄时的转运体丰度，也不会影响近端肾小管钠/氢交换器或远曲小管钠氯共转运蛋白的蛋白丰度。与同龄同性别的对照组相比，产前地塞米松组的系统性肾素或醛固酮无差异。总之，雄性而非雌性后代在产前地塞米松的作用下血压和尿蛋白排泄增加。产前编程引起的血压升高与肾管状转运蛋白的丰度增加不一致，也与血浆肾素活性和血清醛固酮无关。
