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37: Administration of 17OH progesterone attenuates TNF alpha-induced hypertension during pregnancy

      Objective

      Increases in inflammatory cytokines may be an important link between placental ischemia, endothelial dysfunction, and hypertension in women with preeclampsia. We have previously demonstrated that a 2-fold increase in circulating TNFα increases mean arterial pressure (MAP) in the pregnant rat. The objective of this study was to examine the role of 17-OHP, a known anti-inflammatory agent, in attenuating TNFα-induced hypertension in gravid rats.

      Study Design

      Sprague-Dawley rats were anesthetized on Day 14 of pregnancy and underwent either 1) anesthesia; 2) injection of intraperitoneal progesterone (.83mg); 3) mini-osmotic pump infusing TNFα (50 ng/day); or 4) injection of intraperitoneal progesterone and mini-osmotic pump infusing TNFα. On day 18, carotid artery catheters were inserted; on day 19 MAP, maternal and pup weights were measured. Blood, kidneys and placentas were collected. Plasma was analyzed for circulating progesterone and TNFα.

      Results

      TNFα administered to normal pregnant rats significantly increased MAP from 103+/−2 to 115 +/−3 mmHg (p<0.01) with a two-fold increase in circulating TNFα (23+/−8 vs. 47+/− 7pg/ml). However, MAP did not increase in response to a 2-fold increase in TNFα in pregnant rats receiving 17-OHP (98 +/−3 17-OHP vs. 100 +/− 4 mmHg 17-OHP+TNFα). There was no significant difference in weight gain, litter size or placenta weight among any of the groups.

      Conclusion

      Administration of 17-OHP attenuates TNFα-induced hypertension in the pregnant rat model without significantly affecting maternal weight gain, litter size, pup size or placental size. These results suggest that 17-OHP may be a viable option for treatment of hypertension associated with elevated cytokine levels in preeclamptic women.