In inpatient studies of normotensive and hypertensive black and white subjects, we will investigate the hypothesis that a diet marginally adequate with respect to potassium, 30 meq/day, will induce or exacerbate the phenomenon of salt-sensitivity, as determined by the magnitude of increase in blood pressure when dietary sodium chloride is increased from 40-250 meq/day for a period of 9 days. To determine whether the marginally adequate dietary potassium caused the occurrence or exacerbation of the salt-sensitivity, we will correct the mild potassium depletion induced by supplementing dietary potassium for a 9 day period with 40 mmol, of potassium bicarbonate (KHCO3) to increase intake to normal, 70 meq/day, while the NaCl level is continued. The effect on blood pressure of the supplement of potassium and its discontinuance will be determined. We have already determined that the small change in dietary potassium over the low-normal range, 30-70 meq/day, significantly modulates the blood pressure response to dietary NaCl, a NaCl-induced increase in blood pressure significantly reversing with the supplement of KHCO3 and rapidly reoccurring after discontinuance of the supplement of KHCO3. The supplement of KHCO3 induced a substantial increase in the plasma potassium, but only a minimal increase in the morning fasting period. The potassium supplement also induced a substantial natriuresis and loss of weight, the renal hemodynamic correlates of which will be investigated. We will determine, whether salt sensitivity induced or exacerbated, by marginally adequate dietary intake of potassium is attended by: 1) increased arterial stiffness, as assessed by an increased pulse wave velocity; 2) augmented systolic peak blood pressure in the aortic arch, as assessed by the carotid artery pulse wave form determined by applanation tonometry; 3) enhanced arterial pressor response to intravenous administration of norepinephrine; 4) increased forearm arterial resistance and reduced forearm blood low; 5) reduced vasorelaxation in response to intraarterial acetylcholine and 6) enhanced response to intraarterial phentolamine. Given the evidence that the hypertensive effect of NaCl requires its chloride component as well as Na, and given the renal vasopressor effect of chloride per se, we will test the hypothesis that the chloride component of KCl constrains its capacity to attenuate hypertension. In a placebo controlled, double blind outpatient study of black men and women with increased hypertension, we will determine whether orally administered KHCO3 is more effective than KCl in lowering blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL047943-03
Application #
3367111
Study Section
Special Emphasis Panel (SRC (SE))
Project Start
1991-09-30
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
3
Fiscal Year
1993
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
Schmidlin, Olga; Tanaka, Masae; Sebastian, Anthony et al. (2010) Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis. J Hypertens 28:87-94
Morris Jr, R Curtis; Schmidlin, Olga; Frassetto, Lynda A et al. (2006) Relationship and interaction between sodium and potassium. J Am Coll Nutr 25:262S-270S
Schmidlin, Olga; Tanaka, Masae; Bollen, Andrew W et al. (2005) Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat. Hypertension 45:867-73
Ma, Yunn-Hwa; Wei, Hsiao-Wen; Su, Kwan-Hwa et al. (2004) Chloride-dependent calcium transients induced by angiotensin II in vascular smooth muscle cells. Am J Physiol Cell Physiol 286:C112-8
Tanaka, M; Schmidlin, O; Olson, J L et al. (2001) Chloride-sensitive renal microangiopathy in the stroke-prone spontaneously hypertensive rat. Kidney Int 59:1066-76
Morris Jr, R C; Schmidlin, O; Tanaka, M et al. (1999) Differing effects of supplemental KCl and KHCO3: pathophysiological and clinical implications. Semin Nephrol 19:487-93
Morris Jr, R C; Sebastian, A; Forman, A et al. (1999) Normotensive salt sensitivity: effects of race and dietary potassium. Hypertension 33:18-23
Schmidlin, O; Forman, A; Tanaka, M et al. (1999) NaCl-induced renal vasoconstriction in salt-sensitive African Americans: antipressor and hemodynamic effects of potassium bicarbonate. Hypertension 33:633-9
Frassetto, L A; Todd, K M; Morris Jr, R C et al. (1998) Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr 68:576-83
Sudhir, K; Forman, A; Yi, S L et al. (1997) Reduced dietary potassium reversibly enhances vasopressor response to stress in African Americans. Hypertension 29:1083-90

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