Abstract P3039: Altered Maternal and Fetal Vasopressin Receptors in Response to Hypertensive Stress in Pregnancy

Abstract

Children born to women with hypertensive disorders in pregnancy have an elevated risk of developing hypertensive disorders later in life. The mechanisms for this fetal programming are unclear. Because vasopressin (AVP) is a hormone that functions to regulate blood pressure and volume homeostasis, we hypothesized that differences in expression of vasopressin receptors (AVPRs) and related genes are also altered in children born from preeclampsia-affected pregnancies. We measured the expression of receptors AVPR1a, AVPR1b, AVPR2, OXTR, and CUL5 as well as LNPEP, the major aminopeptidase that cleaves AVP. Expression in umbilical cord blood cells and maternal peripheral blood cells from women with 1) no hypertensive disorders in pregnancy (control subjects) (N=20) 2) pregnant women with chronic hypertension (N=20) and 3) women with preeclampsia (N=10) in the index pregnancy were compared. Coded cell samples and associated clinical data were obtained from the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784). RNA was purified from the cells and used for real-time quantitative PCR to assess variation in receptor expression in children born to women with hypertensive disorders of pregnancy relative to control subjects. In children born to women with chronic hypertension, AVPR2 (-8.2 Fold Change, P<0.001), LNPEP (-13 Fold Change, P<0.001), CUL5 (-14 Fold Change, P<0.001), AVPR1b (-3.1 Fold Change, P=0.001), and OXTR (-4.3 Fold Change) were all significantly under-expressed when compared to normotensive controls. Samples from children born to women with preeclampsia had significantly lower expression of AVPR1a (-4.7 Fold Change, P<0.001), AVPR1b (-2.5 Fold Change, P=0.045), AVPR2 (-2.5 Fold Change, P=0.001), and OXTR (-2.8 Fold Change, P<0.001) when compared to non-preeclamptic samples. Differences in expression were also mirrored early in pregnancy in maternal blood in women with chronic hypertension. For example, CUL5 and LNPEP were decreased in the first trimester (-3.01 Fold Change, P=0.004 and -3.64 Fold Change P=0.007, respectively). The differences in gene expression in cord blood may be related to the future risk of hypertension later in life for children born to women with hypertensive diseases in pregnancy.