A primary role for the kidney in the initiation and maintenance of hypertension (HTN) has long been recognized, but the pathogenetic interactions among renal hemodynamics, hormonal and hereditary factors, and dietary sodium intake remain enigmatic. Reduction in filtration surface area, whether acquired in the course of intrinsic renal disease or after surgical renal ablation, leads to systemic hypertension (HTN) as well as to progressive renal failure, sequelae made even more severe by dietary sodium excess. HTN is also commonly observed in certain inbred rat strains in which filtration surface area is congenitally deficient. We postulate that a renal abnormality which contributes to HTN is a reduced number of nephrons, the consequence of which is limitation in the ability to excrete sodium, and thus, salt-sensitive hypertension. Congenitally reduced filtration surface area may also explain why only some, but not all, patients who acquire renal disease eventually go on to renal failure, and may also account for the susceptibility of a subset of diabetic patients to develop overt glomerulopathy. Clinically, tests of renal reserve capacity may serve as a useful guide to identification of patients at risk for the development of HTN and progressive renal disease. Accordingly, this proposal aims to investigate the role of a reduction in filtration capacity in the pathogenesis of HTN and progressive renal disease in the rat. Susceptibility to HTN, role of sodium intake, and risk of progressive glomerular injury will be studied in normotensive rats in which glomerular number is experimentally modified, as well as in HTN-prone rat strains with congenitally reduced nephron numbers. Correlations of glomerular number and filtration capacity with HTN, sodium intake, rate of progression of renal disease, vasoactive hormones, and renal reserve capacity will provide new insights into conceptual and practical approaches to treatment of patients with HTN and progressive renal disease.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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