The objective of this proposal is to define the mechanisms mediating hypertension in a model of pregnancy-induced hypertension produced by chronic reduction in uterine perfusion pressure in pregnant rats. The central hypothesis to be tested in this proposal is that a reduction in uteroplacental perfusion pressure causes hypertension by reducing renal-pressure natriuresis. The reduction in pressure natriuresis occurs as a result of tumor necrosis factor causing endothelial cell activation that leads to enhanced formation of endothelin. These abnormalities reduce renal plasma flow and glomerular filtration thereby decreasing renal sodium excretory function. To test this hypothesis, arterial pressure, renal and endothelial function will be examined in a conscious, chronically instrumented rat model of chronic PIH produced by long-term reduction in uterine perfusion pressure.
Specific aims to be addressed are: 1) To test the hypothesis that abnormalities in cardiovascular and renal function during chronic reductions in uteroplacental perfusion pressure are due to elevations in maternal plasma TNF alpha; 2) To test the hypothesis that endothelin plays an important role in mediating TNF alpha-induced abnormalities in cardiovascular and renal function in pregnant rats; 3) To test the hypothesis that estrogens and/or progesterone enhance the endothelial activation and hypertensive response to TNF alpha.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HL076145-01
Application #
6745394
Study Section
Special Emphasis Panel (ZRG1-SCS (29))
Program Officer
Schucker, Beth
Project Start
2004-03-29
Project End
2007-03-28
Budget Start
2004-03-29
Budget End
2005-03-28
Support Year
1
Fiscal Year
2004
Total Cost
$26,522
Indirect Cost
Name
University of Mississippi Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
LaMarca, Babbette D; Chandler, Derrick L; Grubbs, Lee et al. (2007) Role of sex steroids in modulating tumor necrosis factor alpha-induced changes in vascular function and blood pressure. Am J Hypertens 20:1216-21
Gadonski, Giovani; LaMarca, B Babbette D; Sullivan, Elizabeth et al. (2006) Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of interleukin 6. Hypertension 48:711-6