Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: Effect of IL‐6 blockade.

Abstract

Placental ischemia plays an important role in the pathogenesis of hypertension in preeclamptic women. Increases in inflammatory cytokines have been proposed to be an important link between placental ischemia, endothelial dysfunction, and hypertension. Our laboratory has developed a novel disease model in which hypertension develops in response to Reductions in Uterine Perfusion Pressure (RUPP) induced during late gestation in the pregnant rat. Mean arterial pressure increases from 105 + 1 mmHg in normal pregnant rats to 129 + 2 mm Hg in RUPP rats. The increase in blood pressure is associated with enhanced cytokine production. The purpose of this study was to determine the role of IL-6 in mediating the increase in blood pressure in response to reductions in uterine perfusion. IL-6 levels increased from 67 + 14 pg/ml in normal pregnant rats to 121 + 13 pg/ml in RUPP rats. Intraperitoneal injections of a monoclonal IL- 6 antibody (10 ug/kg/day) to normal pregnant and RUPP rats were performed on day 17 or day 18 of gestation. Circulating IL-6 levels decreased in RUPP rats from 121 + 13 pg/ml to 66 + 15 pg/ml in those receiving injections on day 17 and to 70.1+ 8.9 pg/ml in those receiving the monoclonal IL-6 antibody on day 18. Monoclonal IL-6 antibody administration had no effect on mean arterial pressure in RUPP rats (129+ 2 mmHg vs 130 + 2 mmHg). In summary, although the increase in blood pressure in response to reductions in uterine perfusion in pregnant rats is associated with increases in plasma IL-6 levels, lowering circulating IL-6 levels in RUPP rat with a monoclonal IL-6 antibody had no effect on arterial pressure.