The incidence of essential hypertension is much greater in American blacks than in whites. The great majority of hypertension in blacks belongs to the salt-sensitive type which can be controlled with diuretics alone. To explain this greater incidence, a """"""""thrifty gene"""""""" has been postulated which promotes renal sodium retention and results in altered sodium homeostasis under conditions of high salt intake. The underlying hypothesis for this proposal is the existence of a different set point for sodium reabsorption in the proximal tubule of individuals with the """"""""thrifty gene"""""""", either under baseline or hormone-regulated conditions. To test this hypothesis, human proximal tubular cells will be expanded in-vitro by primary culture and immortalization techniques and the sodium metabolism of these cells probed in-vitro. Intracellular sodium concentrations will be measured with the fluorescent probe SBFI and video-enhanced imaging techniques. Sodium metabolism will be evaluated by measuring the influence of hormones on intracellular sodium concentrations and changes in the activity of the major sodium transporters (Na,K-ATPase, Na/H exchanger, Na-(HCO3)3 co-transporter). Transporter activity will be determined from rates of sodium concentration changes after addition of appropriate inhibitors (ouabain, EIPA, SITS). The major hormones of interest are angiotensin II, adrenergic agents, natriuretic peptide, parathyroid hormone, bradykinin and eicosanoids. To evaluate whether differences in proximal tubular properties exist that possibly pertain to hypertension in blacks, human material will initially be selected from two groups: a) blacks with a family history of hypertension, and b) non-hypertensive whites with no indication for hypertension in the family. For the analysis, multivariate correlation will be employed between parameters of sodium metabolism measured in-vitro and the relevant clinical or family history data pertaining to hypertension. Preliminary experiments will be carried out with renal proximal tubule cells from the spontaneously hypertensive SHR and the normotensive control WKY rats.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL050173-02
Application #
3369174
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1992-09-30
Project End
1995-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106