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Effect of Aging on Plasma Renin and Aldosterone in Normal Man PETER WEIDMANN, SYLVIANNE DE MYTTENAERE-BURSZTEIN, MORTON H

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Effect of Aging on Plasma Renin and Aldosterone in Normal Man PETER WEIDMANN, SYLVIANNE DE MYTTENAERE-BURSZTEIN, MORTON H View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 8, (1975), p. 325—333 Effect of aging on plasma renin and aldosterone in normal man PETER WEIDMANN, SYLVIANNE DE MYTTENAERE-BURSZTEIN, MORTON H. MAXWELL and JosE DE LIMA Nephrology and Hypertension Service, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, California Effect ofaging on plasma renin and aldosterone in normal man. sential hypertension has been diagnosed more com- Theinfluence of aging on the renin-angiotensin-aldosterone system monly in older than young adults [1—4], and the syn- was evaluated by comparing young (20 to 30 yr) with elderly (62 to 70 yr) healthy subjects. Despite comparable body sodium-fluid drome of hyporeninemic hypoaldosteronism has been balance in the two age groups, serum renin concentration, plasma described almost exclusively in patients older than 50 renin activity and aldosterone concentrations were lower in the elderly. The age-related decreases in circulating renin and aldo- yr of age [5]. sterone concentrations were slight while subjects were supine and The possibility that aging may influence renin and receiving normal sodium intake; when upright and during sodium aldosterone metabolism has been considered pre- depletion, they were more pronounced. Inverse renin-blood pres- sure interrelations were noted during two of four study conditions viously, but the available data on the relationship be- involving normal sodium intake or mild sodium depletion (r = tween age and the function of the renin-angiotensin-al- —0.44and —0.47, respectively), but not during progressive sodium dosterone system in normotensive healthy adults are depletion. Plasma renin levels were decreased in the elderly regard- less of the presence or absence of an inverse relationship with limited and conflicting [2, 4, 6, 7]. The present study blood pressure. Aldosterone and cortisol responses to corticotropin was undertaken to further investigate this question by infusion were unaltered in the elderly. It is concluded that aging comparing plasma renin and aldosterone concentra- may cause a decrease in circulating renin, with parallel lowering of plasma aldosterone concentrations. tions under basal conditions and during stimulation with upright posture, sodium/volume depletion or Effetdu vieillissement sur les concentrations de refine et corticotropin infusion in young and elderly healthy l'aldostérone chez l'homme normal. L'influence du vieillissementsur Icsystème rCnine-angiotensine-aldostérone a été dvaluée par Ia corn- subjects. paraison de sujets normaux jeunes (20 a 30 ans) et de sujets âgés (62 a 70 ans). Malgré un bilan hydro-sodique comparable dans les deux groupes d'áges, Ia concentration sérique de refine, l'activité refine Methods du plasma et Ia concentration d'aldostérone sont inférieurs chez les sujets ages. La diminution liée a l'age de Ia refine et de l'aldostérone Twogroups of normal volunteers were studied. One circulantes est minime quand les sujets sont couches et ont un ap- group included six women and six men, ranging in age port de sodium normal; elle est plus prononcée en orthostatisme et au cours de Ia déplétion en sodium. Des relations inverses from 20 to 30 yr. The other group consisted of four rénine-pression artérielle ont été observées dans deux des quatre sit- women and three men, ranging in age from 62 to 70 yr. uations expérimentales associant un apport normal de sodium ou None of the participants had significant physical ab- une déplétion de sodium modérée (r =-0,44et r =—0,47,respec- tivement). Ces relations n'ont pas été observées au cours de Ia normalities and each was found to have a blood pres- depletion progressive en sodium. La refine est diminuee chez les su- sure of less than 140/90 mm Hg, normal concentra- jets indépendamment de Ia presence ou de l'absence d'une rela- tions of plasma creatinine and electrolytes and blood tion inverse avec Ia pression artérielle. Les reponses du cortisol et de l'aldostérone a Ia corticotrophine ne sont pas modiflées chez Ic sujet urea nitrogen, and normal urine values before entering age. II est conclu que Ic vieillissement peut entrainer une diminution the study. None were taking drugs. de Ia refine circulante avec une diminution parallèle des concentra- All studies were done while the subjects were receiv- tions d'aldosterone. ing a defined daily intake of either 120 mEq of sodium Diminished levels of circulating renin occur in sev- and 60 mEq of potassium ("normal sodium intake") eral pathologic states, but the factors responsible for or 10 mEq of sodium and 60 mEq of potassium ("re- this have not been fully elucidated. The incidence of at stricted sodium intake"). Body weight, urinary sodium least two hyporeninemic disorders appears to increase and potassium excretion, and creatinine clearance with advancing age. More specifically, low-renin es- were measured daily throughout the study. Blood pressure; serum renin concentration; plasma renin ac- Received for publication March 4, 1975; tivity; and aldosterone, sodium and potassium concen- and in revised form June 24, 1975. trations were determined in each subject in both the © 1975, by the International Society of Nephrology. supine and upright positions (each position for one 325 326 Weidmann et a! hour): a) after three days of normal sodium intake (in Haber et al using 8-hydroxyquinoline and dimercaprol the young subjects this was done twice); b) after three as protective agents [9]; each sample was measured at days of restricted sodium intake; c) after six days of two incubation conditions, i.e., at pH 7.4 and 5.7. restricted sodium intake; and d) after seven days of re- Plasma aldosterone was measured by the radio- stricted sodium intake and oral administration of fu- immunoassay method of Ito et al [10] and plasma cor- rosemide, approximately 1.2 mg/kg of body wt, at 5 tisol by competitive protein binding [11]. Plasma vol- PM on the seventh day of sodium restriction. Following ume was measured with '251-human serum albumin; three days of normal sodium intake and six and seven the radioactivity level of peripheral venous blood vol- days of sodium depletion, measurements of plasma ume was used to calculate whole blood volume by as- and blood volume were also performed. This part of suming the following: the study extended over ten days. Eight young and all whole blood volume =measuredvolume X seven elderly subjects participated in a second part, 100—hematocrit in which the response to a two-hour infusion of a 100—0.91 x hematocrit synthetic adrenocorticotropic hormone (Cortrosyn, [ Organon Inc.) at a rate of 0.1 mg/hr (approximately A paired data I test was used for statistical com- parison of measurements obtained from the young or 10 USP U of ACTH) was studied following three days elderly group before and during the various study con- of normal sodium intake: blood pressure; serum renin ditions; an unpaired data I test was applied for com- concentration and plasma renin activity; and aldoster- one, cortisol, sodium and potassium concentrations parison of the two age groups. In our previous studies, absolute plasma renin and aldosterone concentrations were measured before (8 AM) and after one and two were always found to be abnormally distributed, with hours of ACTH infusion. Blood pressure was determined with a standard an approximately normal distribution following loga- rithmic transformation of these values [12, 13]. This sphygmomanometer and pressure cuff, with the first was systematically reexamined and found to be also Korotkoff sound being recorded as systolic pressure and the fifth sound as diastolic pressure. Supine and true in the present study. Therefore, natural loga- rithms of the serum renin concentration, plasma renin upright measurements were always obtained after the activity and aldosterone values were utilized for all subjects had remained in these positions for one hour. statistical calculations involving a t test or linear re- Three values were recorded and averaged. Mean pres- sure was calculated as the sum of diastolic pressure gression analysis. and one-third of the pulse pressure. Plasma sodium Results and potassium concentrations were measured with a flame photometer (Instrumentation Laboratory). Se- Fluid and electrolyte status, and glomerularfiltra- rum renin concentration was determined by radio- lion rate (Table 1 and Fig. 1). Plasma sodium concen- immunoassay, using a modification of the method of trations measured before and during different degrees Gould, Skeggs and Kahn [8]. Plasma renin activity of sodium depletion were comparable in the young was determined by the radioimmunoassay method of and elderly subjects (Table 1). Table I. Plasma sodiumand potassium concentrationsand plasma and blood volumes in 12 young and 7 elderly subjects during normal sodium intake and after sodium depletion (mean SD) Normal Naa Low Nabx 3 days Low Nab>< 6 days Low Nabx 7 days + FC Young Elderly Young Elderly Young Elderly Young Elderly Plasma sodium, mEq/liter Supine 140.5 2.0 139.6 1.5 139.02.4136.63.0139.42.2 139.0 1.4 139.4 1.7 139.0 1.3 Upright 140.1 0.8139.0 1.7 138.8 3.4 137.1 3.1 139.9 2.1 138.1 1.7 139.5 1.7 138.3 1.0 Plasma potassium, mEq/lizer Supine 4.150.234.120.244.04 0.304.07 0.19e4.040.294.31 0.40 3.75 0.36e 3.900.27e Upright 4.34 0.384.25 0.344.200.164.34 0.17e4.12 0.254.48 3.92 0.244.21 0.l9 Plasma volumed,ml/cm 14.4 2.5 15.3 3.3 — — 13.5 2.5 14.4 31g 13.0 l.7g 13.9 + 25g Blood volume0, mi/cm 24.44.6 25.1 5.5 — — 22.5 52g 24.0 50g22.0 3.8 23.1 50g aNormal Na =sodiumintake of 120 mEq/day.
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