Plasma Renin Activity in Relation to Serum Sodium Concentration and Body Fluid Balance H. H. NEWSOME AND F. C. BARTTER Endocrinology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland 20014 ABSTRACT. The relationship of peripheral tivity decreased (109 to 62 ng/100 ml) during plasma renin activity to changes in body fluid overhydration in spite of a decrease (140 to volume and to serum sodium concentration was 129 mEq/1) in serum sodium concentration. Downloaded from https://academic.oup.com/jcem/article/28/12/1704/2715533 by guest on 29 September 2021 studied in normal subjects and in hypertensive Expansion of intravascular volume in a patient patients during changes in hydration or changes with a defect in renal sodium conservation re- in sodium intake. There was an inverse relation- sulted in suppression of plasma renin activity. ship between renin activity and fluid volume; It thus appears that some factor related to body e.g., renin activity increased (168 to 833 ng/100 fluid balance, perhaps intravascular volume, may ml in normal subjects) following loss of body be more important than serum sodium concentra- fluid (—2.1%) by diuresis. In contrast, the tion in determining plasma renin activity. (J relationship of renin activity to serum sodium Clin Endocr 28: 1704, 1968) concentration could be reversed; e.g., renin ac- INCE the relationship of the renin-an- sodium intake; diuretics were administered S giotensin system to the adrenal cortex during the period of lowest sodium intake. was postulated in 1958 (1) and later con- Changes in water balance. Six normal volunteers firmed (2-6), the regulation of renin se- were placed on a diet containing each day 109 cretion has received increasing attention. mEq of sodium (Na) and 500-800 ml total Several factors have been implicated in water (water content of foodstuffs and water of the control of plasma renin concentration. oxidation, combined). During the'control peri- It has been shown that plasma renin is in- ods a constant amount (1000-1500 ml) of extra water was given to each subject. Dehydration versely related to sodium intake (7) and to was effected by withdrawal of the extra water serum sodium concentration (8). It is clear for 48 to 96 hr. Overhydration was established by that other factors such as fluid balance increasing the daily water intake to 2000 to may be involved (9-11). The present study 3000 ml and by administering Pitressin tannate examines the relative roles of serum sodium in oil intramuscularly twice daily. The subjects remained throughout the study in an air-con- concentration and of body fluid volume in ditioned environment. Normal, moderate phys- the control of plasma renin activity. The ical activity was permitted. Body weight, blood results of the study suggest that changes in hemoglobin and hematocrit, blood urea nitro- body fluid volume may supersede serum gen, and serum sodium, potassium, chloride and sodium concentration as a determinant of carbon dioxide content were determined daily. Peripheral plasma renin activity was measured plasma renin activity. in the venous blood of each subject during periods of normal hydration, dehydration and Materials and Methods overhydration. Plasma renin activity was measured in 15 subjects under various conditions of water and Changes in sodium balance. The 5 normal vol- of sodium balance. Changes in water balance unteers and 4 patients with benign hyperten- were accomplished in 6 normal volunteers by sion were maintained on constant daily water overhydration and dehydration; Pitressin tan- intake and studied while each received high nate in oil was administered during the periods (240 mEq), moderate (109 mEq) and low of overhydration. Changes in sodium balance (9 mEq) amounts of dietary Na. While receiv- were accomplished in 5 normal volunteers and 4 ing 9 mEq of sodium daily, the subjects were patients with hypertension by changing the given Mercuhydrin intramuscularly (1 or 2 ml each day). All other conditions and analyses Received January 5, 1968; accepted August 7. were the same as those of the preceding group. 1704 December 1968 RENIN, SERUM SODIUM AND FLUID BALANCE 1705 TABLE 1. Effect of changes in hydration on renin activity, serum sodium and changes in body weight in six normal subjects Hydration— Norm Under Over Norm Under Over Norm Under Over Under Over Renin activity Serum sodium Changes in body weight Supine Upright mEq/1 % Change ng/100 ml B.S. 145 166 94 140 144 126 -2.14 +3.60 C.J. 145 215 64 141 140 132 -2.58 +2.90 E.J. 101 162 30 140 146 127 -1.64 +3.61 L.C. 91 134 107* 255 401 207 140 144 125 -1.95 +2.91 Downloaded from https://academic.oup.com/jcem/article/28/12/1704/2715533 by guest on 29 September 2021 L.B. 146 143 39 302 878 38 140 148 130 -2.22 +4.91 G.T. 72 450 78 267 743 151 139 147 128 •3.41 +3.61 * Overhydration not optimally achieved due to emesis. Peripheral plasma renin activity was measured The pressor responses obtained in the rats in the venous blood of each subject during the were analyzed statistically by the method of period of high-sodium intake (240 mEq), of Bliss (13). Data analysis was facilitated by use normal sodium intake (109 mEq) and of low of a Honeywell 360 computer. A check for sodium intake (9 mEq). Renin activity was parallelism between dose-response curves of assayed during the period of low-sodium intake standard and unknown was done for each only after administration of Mercuhydrin. sample. Results, expressed in ng of angiotensin in 100 ml of plasma (ng/100 ml plasma + SEM), Albumin infusion. A study was done in a patient represent the amount of angiotensin generated (E.M.) with hypertension, arteriolonephro- from endogenous substrate by endogenous renin sclerosis, and a slightly impaired ability of the in 3 hr of incubation at 37 C. Mean recovery for kidney to conserve sodium on a low-sodium the method, when angiotensin was added to diet. Daily Na intake was 109 mEq for 8 days, plasma from nephrectomized dogs, was 31 + followed by 9 mEq for 8 days. At the end of the 13% (SD). The results presented in this paper period of 9 mEq of Na intake 75 g of human were not corrected for recovery. In an estimate serum albumin (9 mEq Na) was given intra- of precision, values from 5 aliquots of pooled venously. Plasma renin activity, serum Na plasma with a mean potency of 1111 ng/100 ml concentration and urinary Na were measured showed a standard deviation of 34 ng/100 ml. immediately before and after albumin infusion No pressor activity was detected in the plasma and several times thereafter. Body weight was from 3 nephrectomized patients awaiting renal recorded daily. transplants. No pressor activity was detectable when epinephrine (100 /xg/100 ml), norepine- Measurement of plasma renin activity. Blood phrine (100 jug/100 ml), or Pitressin (10 mU/ samples were drawn with the subjects either in 100 ml) had been added to the plasma. the supine position at 8 AM and/or in the up- right position at 12 noon. The subjects were Results kept supine for 8 hr or remained up and about for 4 hr before blood sampling. Changes in water balance. An individual Plasma renin activity was determined by a study on changes in water balance in a nor- modification of Boucher's method (12). The mal subject is shown in Fig. 1, and all the modifications are as follows: data on six normal subjects are summarized in Table 1. During the dehydration period in 1. The material was eluted from the column E.J. (Fig. 1) serum Na concentration in- without acidification with acetic acid, and was frozen immediately in a flask immersed in a creased from 140 to 146 mEq/1, renin activ- slurry of dry ice and acetone. ity increased from 101 to 162 ng/100 ml, 2. The frozen material was lyophilized and while body weight decreased by 1.64%. washed 3 times with 80 % ethanol. With dehydration (Table 1), renin activity 3. Three aliquots of each sample were injected into at least 3 rats and compared in each rat (supine and upright) was increased in every with 3 doses of standard Val-5, angiotensin subject except L.B., at a time when serum amide (Ciba), according to a 6-point bioassay Na concentration had increased or re- design. mained the same and body weight had con- 1706 NEWSOME AND BARTTER Volume 28 HYDRATION J.C.. 0. E.J.,0. No INTAKE 07-12-87 Normal Under Over 06-66-78 April 1966 Nov. 1966 H2O 240 109 9+Hq (mEq/d) INTAKE SERUM 140, PITRESSIN Na mEq/1 135 V... 145 250 No 13 5 200 URINARY mEq/l 125 150 Downloaded from https://academic.oup.com/jcem/article/28/12/1704/2715533 by guest on 29 September 2021 Na 100 50 URINARY IOO l- Na L 0 mEq/d 0 L 63 B.W. 61 55 kg B.W. 59 53 •x/ 1500 si 1000 200 500 s RENIN 0 150 ACTIVITY RENIN 3000 100 ng% ACTIVITY U 20001- 50 1000 ng% \ 0 0 I 3 5 7 I 2 DAYS FIG. 2. Effect of changes in sodium intake on serum FIG. 1. Effect of changes in hydra tion on serum Na, urinary Na, body weight and renin activity sodium (Na), urinary sodium (Na), body weight in the supine and in the upright positions in a nor- (B.W.) and renin activity in the supine position in mal subject. Na depletion was accomplished by an a normal subject.