16: 17 OH progesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats

Abstract

Reduction in uteroplacental perfusion (RUPP) is hypothesized to be the initiating factor for the development of hypertension during pregnancy. The objective of this study was to determine if 17OH Progesterone is a promising treatment for hypertension in response to placental ischemia in the pregnant rat. Arterial pressure (MAP) and endothelial factors were examined in a conscious, chronically instrumented rat model of RUPP with or without 17 OHP administration. Hypertension produced by RUPP is associated with endothelial dysfunction, enhanced ET-1 and ROS production, decreased NO synthesis, and a hypertensive shift in the pressure natriuresis relationship. Sprague-Dawley rats were anesthetized on Day 14 of pregnancy and underwent either 1) examination under anesthesia; 2) RUPP: the lower abdominal aorta was isolated and clipped (0.203mm ID) above the iliac bifurcation; branches of both the right and left ovarian arteries were clipped (0.100mm ID) 3) injection of intraperitoneal 17OHP, or 4) RUPP + injection of intraperitoneal 17OHP. On day 18, carotid artery catheters were placed in each rat; on day 19 MAP, maternal and pup weight were measured. Blood, kidneys and placentas were collected and weighed. MAP increased 23 mmHg in RUPP rats compared to control pregnant rats (126 +/−2 vs 103 +/−2 mmHg (p<0.03)). However, RUPP rats receiving progesterone displayed a 16 mmHg increase in MAP (119+/−2 (P0.03). ET-1 increased 3 fold in the cortex from RUPP rats (2.5 + 0.49 relative units, n=6) compared to normal pregnant rats(−1.5 + 0.9 relative units, n=6) (P<0.02) but was −0.6 relative units (n=4) in RUPP + 17 OHP. There was no change in maternal, pup or placental weights in response to 17 OHP administration in RUPP rats. Administration of 17 OH Progesterone blunts the hypertension associated with RUPP in pregnant rats possibly via protecting against endothelial activation that is associated with placental ischemia.