The concept of """"""""sodium-dependent"""""""" hypertension is based almost entirely on studies in which the dietary intake of sodium (Na+) has been varied by varying the intake of sodium chloride (NaC1). The dietary intake of chloride might also be a determinant of blood pressure (BP). If so, """"""""hidden"""""""" sources of dietary Na+ such as sodium bicarbonate (NaHCO3) or sodium ascorbate may be as important in the pathogenesis of hypertension as has been widely believed. In chronic metabolic balance studies in patients with """"""""salt-sensitive"""""""" essential hypertension, in spontaneously hypertensive rats, and in rats with a reduction in functional renal mass, we will determine whether changes in dietary NaC1 induce changes in blood pressure different from those induced by changes in dietary sodium citrate, bicarbonate, or ascorbate. The changes in body weight, extracellular fluid volume, and external balances of sodium, potassium, chloride, calcium, magnesium, and phosphorus induced by changing the intake of the different sodium salts will also be determined. In uninephrectomized rats given desoxycorticosterone (DOC), we will attempt to determine whether the finding that a normal amount of dietary NaC1 induces hypertension, whereas an equimolar amount of dietary NaHCO3 does not, is due to a hypertensive effect of chloride, or to an anti-hypertensive effect of bicarbonate. Accordingly, in uninephrectomized rats given DOC, we will determine; 1) whether supplemental dietary NaHCO3 can attenuate the hypercalciuric and hypertensive effects of a normal amount of dietary NaC1; 2) whether a non-halide Na+ salt that does not induce the severe alkalosis induced by NaHCO3 (e.g. sodium caseinate), still fails to induce hypertension; 3) whether a normal amount of dietary NaC1 gives rise to a serum level of parathyroid hormone (PTH) greater than that which attends an equimolar amount of dietary NaHCO3 and whether exogenously administered PTH can induce hypertension in rats given this amount of NaHCO3; 4) whether the antihypertensive effect of supplemental dietary calcium carbonate is greater than that of supplemental dietary calcium chloride; 5) whether a normal amount of dietary NaC1 gives rise to greater levels of plasma volume, cardiac output, or sympathetic nervous system activity, or lower levels of vascular smooth muscle sodium-potassium ATPase activity, than those which attend an equimolar amount of dietary NaHCO3.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001490-04
Application #
3081853
Study Section
Research Manpower Review Committee (MR)
Project Start
1985-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
St Lezin, E; Simonet, L; Pravenec, M et al. (1992) Hypertensive strains and normotensive 'control' strains. How closely are they related? Hypertension 19:419-24
Pravenec, M; Simonet, L; Kren, V et al. (1992) Assignment of rat linkage group V to chromosome 19 by single-strand conformation polymorphism analysis of somatic cell hybrids. Genomics 12:350-6
Kurtz, T W; St Lezin, E M (1992) Gene mapping in experimental hypertension. J Am Soc Nephrol 3:28-34
Simonet, L; St Lezin, E; Kurtz, T W (1991) Sequence analysis of the alpha 1 Na+,K(+)-ATPase gene in the Dahl salt-sensitive rat. Hypertension 18:689-93
Pravenec, M; Simonet, L; Kren, V et al. (1991) The rat renin gene: assignment to chromosome 13 and linkage to the regulation of blood pressure. Genomics 9:466-72
Moulinier, L; Venet, T; Schiller, N B et al. (1991) Measurement of aortic blood flow by Doppler echocardiography: day to day variability in normal subjects and applicability in clinical research. J Am Coll Cardiol 17:1326-33
Pravenec, M; Kren, V; Kunes, J et al. (1991) Cosegregation of blood pressure with a kallikrein gene family polymorphism. Hypertension 17:242-6
Kurtz, T W; Casto, R; Simonet, L et al. (1990) Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat. Hypertension 16:718-24
Kurtz, T W; Simonet, L; Kabra, P M et al. (1990) Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure. J Clin Invest 85:1328-32
Kurtz, T W; Montano, M; Chan, L et al. (1989) Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat. Hypertension 13:188-92

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