0021-972X/78/4702-0296$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society

Vol. 47, No. 2 Printed in U.S.A.

Effects of Dietary Potassium and Race on Urinary Excretion of Kallikrein and Aldosterone in Man DAVID HORWITZ, HARRY S. MARGOLIUS, AND HARRY R. REISER Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20014 ABSTRACT. Urinary excretion of kallikrein by 16 normal and 8 hypertensive subjects was studied at three levels of dietary potassium: 85 meq/day for 5 days, 185 meq/day for 7 days, and 25 meq/day for 10 days. Excretion of kallikrein varied directly with potassium intake and paralleled excretion of aldosterone in both normotensive and hypertensive subjects. Mean levels of excretion of kallikrein at 85, 185, and 25 meq intake of potassium were 10.8, 19.1, and 5.8 esterase U/day (EU/day), respectively, for the normotensive subjects and 8.8, 13.9, and 6.1 EU/day for the hypertensive subjects. Mean levels of excretion of kallikrein were


RINARY excretion of kallikrein, a renal enzyme that catalyzes the formation of the potent vasodilator peptide kallidin, is increased by salt deprivation in man and the rat (1-3). We have proposed that such increases in urinary excretion of kallikrein are secondary to changes in levels of aldosterone, for they are reversed by the aldosterone antagonist spironolactone and are induced by administration of fludrocortisone, a synthetic sodium-retaining steroid (1, 2). Further, increased excretion of urinary kallikrein has been found in patients with hyperaldosteronism and reversal has followed removal of aldosterone-producing tumors (2, 4). The objective of the present study was to examine the effects on urinary kallikrein of alterations in dietary potassium, another factor that changes aldosterone production (5, 6). In the course of analyzing our results, we again noted racial influences on kallikrein excretion (7).

Received June 24, 1977. Address requests for reprints to: David Horwitz, M.D., National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N-256, Bethesda, Maryland 20014.

significantly higher in white than in black subjects among normals and hypertensives [13.0 vs. 5.9 EU/day for normals (P < 0.05) and 13.7 vs. 4.0 EU/day for hypertensives (P < 0.05) on the 85 meq/day diet]. The parallel changes in excretion of kallikrein and aldosterone support the hypothesis that changes in effective levels of aldosterone induce changes in the excretion of kallikrein. Because of racial differences in excretion of kallikrein, matched groups should be used for comparisons of the kallikrein system in disease states. (J Clin Endocrinol Metab 47: 296, 1978)

Materials and Methods Subjects The subjects of the study were 16 normal volunteers (9 women, 7 men; 11 white, 5 black) of ages 19-57 yr (mean age, 32 yr) and 8 patients with

uncomplicated moderate essential hypertension (6 men, 2 women; 4 blacks, 4 whites) of ages 27-59 yr (mean age, 45 yr). Each hypertensive patient showed mean diastolic blood pressure levels of at least 99 mm Hg (supine or erect) during multiple daily observations in the first 3 days of hospitalization (mean, 150/106 mm Hg supine); each had serum creatinine levels ^ 1.3 mg% and showed no evidence of a primary etiology for his hypertension after the following tests: iv pyelogram (7), renal arteriogram (2), 24-h VMA excretion, 24-h aldosterone excretion, plasma renin activity, urine culture, urinalysis, and serum electrolytes. The subjects received no medications during or for at least 2 weeks before the study. Each subject gave his written informed consent before participation. The protocol was approved by the peer review committees and the Deputy Director for Science of the NIH. Protocol Sixteen normal and eight hypertensive subjects received a diet containing 25 meq potassium and 10 meq sodium chloride supplemented by 100 meq


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EFFECT OF POTASSIUM ON KALLIKREIN AND ALDOSTERONE sodium chloride in a shaker for 22 days. This was * supplemented by 60 meq potassium chloride syrup daily for the first 5 days and by 160 meq for the next 7 days. Twenty-four-hour urine samples were collected at least every other day in a container with 30 ml toluene and were refrigerated until assayed for kallikrein, sodium, potassium, creatinine, and aldosterone. Blood samples for determi> nation of serum sodium and potassium were drawn at intervals of 2-4 days. Analytical procedures Urinary kallikrein was assayed by the radi* ochemical esterolytic method of Beaven et al. (8), as modified by Margolius et al. (1); the [3H]methanol released after incubation with the synthetic substrate, a-iV-p-tosyl-L-arginine-[3H]methyl ester ^ (TAME), was extracted and counted; excretion of kallikrein per 24 h was calculated from a standard curve based on dilutions of pure human urinary *- kallikrein (kindly supplied by Dr. Jack V. Pierce, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD). Results were expressed in esterase units, i.e. the amount of kallikrein which hydrolyzes 1 /xmol TAME/min at pH 8.0 and 30 C. Aldosterone excretion was measured by the double isotope derivative method of Kliman and Peterson (9). Sodium and potassium were assayed by flame photometry. Paired t tests were employed for comparisons of results at different levels of intake of potassium, whereas unpaired t tests were used for comparisons of racial effects.

Results r

f •f ' ~j


Each of 16 normal subjects showed a rise in the excretion of urinary kallikrein when dietary potassium was increased from 85 to 185 meq/day and a fall when intake was reduced to 25 meq/day (probability of occurrence by chance





16 NORMAL SUBJECTS -f- Mean ±1 S.E.M.


FIG. 1. Changes in urinary excretion of kallikrein in response to changes in dietary potassium in 16 normal subjects.

5 ^ 200


Effects of dietary potassium and race on urinary excretion of kallikrein and aldosterone in man.

0021-972X/78/4702-0296$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society Vol. 47, No. 2 Printed in U...
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