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(Hypertension. 2005;46:1022.)
© 2005 American Heart Association, Inc.

Part 2 Original Articles

Hypertension Produced by Reductions in Uterine Perfusion in the Pregnant Rat

Role of Tumor Necrosis Factor-

B. Babbette D. LaMarca; William A. Bennett; Barbara T. Alexander; Kathy Cockrell; Joey P. Granger

From the Department of Physiology and Obstetrics/Gynecology, University of Mississippi Medical Center, Jackson.

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

Inflammatory cytokines such as tumor necrosis factor (TNF)- are elevated in preeclamptic women and are thought to be an important link between placental ischemia and endothelial dysfunction. The purpose of this study was to determine the role of TNF in mediating hypertension in response to chronic reductions in uterine perfusion (RUPPs) in pregnant rats. Arterial pressure was significantly higher in RUPP rats (138±1 mm Hg) than in pregnant rats (107±1 mm Hg). Serum TNF- levels in the RUPP rats were 17±4 pg/mL compared with 8±1 pg/mL in normal pregnant rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma TNF- on renal and systemic hemodynamics in pregnant rats, we infused TNF- for 5 days at a rate of 50 ng/d during days 14 to 19 of gestation in pregnant rats. Serum levels were 7±2 pg/mL in the control pregnant rats and 14±2 pg/mL in the TNF-–treated pregnant rats. Mean arterial pressure was higher in the TNF-–treated pregnant rats (123±3 mm Hg) compared with pregnant controls (96±3 mm Hg) at day 19 of gestation. TNF- increased renal vascular resistance in pregnant rats by 182%. Renal plasma flow was 5.4±1.2 mL/min in the TNF-–treated group and 9.2±1.6 mL/min in the control group. Glomerular filtration rate was 1.7±0.4 mL/min in the TNF-–treated group and 2.6±0.4 mL/min in the control group. In summary, these data suggest that TNF- may play an important role in mediating the increased arterial pressure in response to chronic RUPPs in pregnant rats.

Key Words: kidney • pregnancy • hypertension, pregnancy • cytokines • endothelin

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