Evidence favoring a role for sodium intake in the pathogenesis of hypertension has arisen from multiple sources. However, it is also clear that therapeutic approaches based on modification of sodium intake or the use of diuretic therapy are only effective in some patients. Our working hypothesis is that sodium-sensitive hypertension is not a homogeneous group, but includes patients with some forms of secondary hypertension (primary aldosteronism bilateral renal artery stenosis, and chronic renal failure), low-renin essential hypertension, and some patients with normal and high-renin essential hypertension. This proposal addresses four specific questions: First, does the blood pressure increment with sodium loading and blood pressure decrement wih diuretic therapy identify the same patient with """"""""salt-sensitive hypertension""""""""? These are the two major criteria for salt sensitivity. Secondly, is there a more simple and precise screening test for salt-sensitive hypertension? Specifically, we plan to assess the level of a number of potentially salt-sensitive biologic indices in normal and hypertensive subjects, including: the ouabain-like inhibitor of sodium/potassium ATPase, a factor which modifies in vitro vascular reactivity, intracellular sodium and/or calcium content and sodium transport in the red cell, platelet angiotensin II (AII) receptor number, and in vivo vascular (particularly renovascular) and adrenal responsiveness to AII. Thirdly, we will examine the effect of changes in dietary sodium intake (sodium dose-response curve) on the above mentioned indices in normal subjects to determine whether there is a hierachical utilization of these various factors as sodium intake changes; is the activation of each an off-on phenomenon of dose related? Finally, we will determine whether the relationship between the level of sodium intake and any of these biologic variables is different between hypertensives versus normal subjects, old versus young, white versus non-white, and whether salt-sensitive hypertensives have a different pattern than salt-insensitive hypertensives. Successful completion of these studies will provide a more rational and practical basis for identifying patients in whom specific recommendations for therapy can be made, provide insight into the mechanism(s) by which sodium intake induces hypertension in some patients, and delineate the underlying abnormalities in these patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036420-03
Application #
3351445
Study Section
(SRC)
Project Start
1985-09-30
Project End
1989-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Williams, G H; Fisher, N D; Hunt, S C et al. (2000) Effects of gender and genotype on the phenotypic expression of nonmodulating essential hypertension. Kidney Int 57:1404-7
Hopkins, P N; Hunt, S C; Wu, L L et al. (1996) Hypertension, dyslipidemia, and insulin resistance: links in a chain or spokes on a wheel? Curr Opin Lipidol 7:241-53
Hopkins, P N; Lifton, R P; Hollenberg, N K et al. (1996) Blunted renal vascular response to angiotensin II is associated with a common variant of the angiotensinogen gene and obesity. J Hypertens 14:199-207
Gaboury, C L; Hollenberg, N K; Hopkins, P N et al. (1995) Metabolic derangements in nonmodulating hypertension. Am J Hypertens 8:870-5
Quinn, S J; Brauneis, U; Tillotson, D L et al. (1992) Calcium channels and control of cytosolic calcium in rat and bovine zona glomerulosa cells. Am J Physiol 262:C598-606
Williams, G H; Dluhy, R G; Lifton, R P et al. (1992) Non-modulation as an intermediate phenotype in essential hypertension. Hypertension 20:788-96
Rich, G M; McCullough, M; Olmedo, A et al. (1991) Blood pressure and renal blood flow responses to dietary calcium and sodium intake in humans. Am J Hypertens 4:642S-645S
Moore, T J; Malarick, C; Olmedo, A et al. (1991) Salt restriction lowers resting blood pressure but not 24-h ambulatory blood pressure. Am J Hypertens 4:410-5
Quinn, S J; Enyedi, P; Tillotson, D L et al. (1990) Cytosolic calcium and aldosterone response patterns of rat adrenal glomerulosa cells stimulated by vasopressin: comparison with angiotensin II. Endocrinology 127:541-8
Williams, G H; Gordon, M S; Stuenkel, C A et al. (1990) Dopamine and nonmodulating hypertension. Am J Hypertens 3:112S-115S

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