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(Hypertension. 2006;47:615.)
© 2006 American Heart Association, Inc.

Part 2 Original Articles

Enhanced Endothelin Synthesis by Endothelial Cells Exposed to Sera From Pregnant Rats With Decreased Uterine Perfusion

Lyndsay Roberts; B. Babbette D. LaMarca; Lillian Fournier; Jennifer Bain; Kathy Cockrell; Joey P. Granger

From the Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Miss.

Correspondence to Joey P. Granger, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail jgranger{at}physiology.umsmed.edu

The initiating event in preeclampsia is thought be to reduced uteroplacental perfusion. Although we have reported previously that chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats results in hypertension and enhanced endothelin production, the factors linking placental ischemia and endothelial cell activation remain unclear. The purpose of this study was to determine the role of angiotensin II type-1 (AT₁) receptor activation on endothelin production induced by serum from pregnant rats exposed to reductions in uterine perfusion. To achieve this goal, human umbilical vein endothelial cells were exposed to sera collected from RUPP rats or normal pregnant rats. Arterial pressure was significantly higher in RUPP rats (135±2 mm Hg) than in pregnant rats (106±1 mm Hg). Six hours after exposure to RUPP serum (n=17), cell media endothelin concentration was 18.4±2.7 pg/mL as compared with 9.22±1.3 pg/mL from cells exposed to serum from normal pregnant rats (n=9). Eighteen hours after exposure to RUPP serum (n=7), endothelin concentration was 30.5±3.8 pg/mL as compared with 12.8±5.3 pg/mL from cells exposed to normal pregnant rat serum (n=6). In contrast, serum from RUPP rats did not increase endothelin production in human umbilical vein endothelial cells pretreated with an AT₁ receptor antagonist, losartan (15 µmol/L). Eighteen hours after exposure to RUPP serum and losartan (n=14), endothelin concentration was 21.3±2.2 pg/mL as compared with 16.4±3.3 pg/mL from cells exposed to normal pregnant rat serum and losartan (n=10). These data indicate that serum from pregnant rats exposed to reductions in uterine perfusion enhances endothelin production by endothelial cells via by AT₁ receptor activation.

Key Words: pregnancy, hypertension • angiotensin II • endothelin

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