002l-972X/79/4801-0026$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1979 by The Endocrine Society
Vol. 48, No. 1 Printed in U.S.A.
Effect of Sodium Intake on Plasma Catecholamines in Normal Subjects* MARK S. ROMOFF, GERALD KEUSCHf, VITO M. CAMPESE, MAW-SONG WANG, ROBERT M. FRIEDLER, PETER WEIDMANN, AND SHAUL G. MASSRY Division of Nephrology and Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
ABSTRACT. The effect of the state of sodium balance on the activity of the sympathetic nervous system has been evaluated previously by measuring urinary catecholamine excretion. Since urinary catecholamine may be affected by factors such as renal function or renal production of catecholamines, blood catecholamines may provide a better index of the activity of the sympathetic nervous system. The present study was undertaken to evaluate the effect of varying sodium intake on blood catecholamines. Thirteen normal subjects were studied for a period of 3 weeks in a metabolic ward. They received during the first, second, and third week 10, 100, and 200 meq sodium/day, respectively. On the seventh day of each week, when the patients had achieved sodium balance, urinary sodium excretion as well as blood levels of PRA, norepinephrine (NE), epinephrine (Ep), and dopamine (D) were measured in the supine position, at 5, 10, 15, and 20 min of upright posture, and at the end of 40 min of ambulation.
S
EVERAL lines of evidence point toward the possible role of increased activity of the sympathetic nervous system in the genesis of essential hypertension (1-3). Esler et al. found hemodynamic evidence of sympathetic hyperactivity in a group of patients with high renin hypertension (4). However, Mitchell et al. (5) did not find differences in plasma catecholamine levels among hypertensive patients with different levels of PRA. The data on the relationship between urinary or blood catecholamines and essential hypertension are controversial. Some investigators have reported elevated levels of urinary catecholamines in 5-33% of patients (6-9), whereas others have found decreased excretion (10). Measurements of blood levels of catecholamines did not reveal a
Received June 5, 1978. Address all correspondence and requests for reprints to: Shaul G. Massry, M. D., Professor of Medicine, Division of Nephrology, University of Southern California, School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033. * This work was presented before the 10th Annual Meeting of the American Society of Nephrology, Washington DC, November 20-22, 1977. It was supported by grants from the American Heart Association Affiliate of Greater Los Angeles (523), a grant from USPHS Service (GCRC RR-43), and a grant from Hoffman-LaRoche Laboratories, Basel, Switzerland. f Supported by the Swiss National Science Foundation.
The results show that: 1) blood levels of NE, Ep, and D as well as PRA were significantly higher during low sodium intake than during medium or high sodium intake, 2) as in the case of PRA, there was an inverse relationship between the blood levels of NE, Ep, and urinary sodium excretion; 3) upright posture produced a significant increment in the blood levels of NE which was not affected by sodium intake; and 4) the increment in PRA with posture was significantly greater during low sodium intake than with medium high sodium intake. The data demonstrate that: 1) the plasma levels of NE, Ep, and D are affected by the state of sodium balance, particularly during marked sodium depletion; and 2) meaningful interpretation of the significance of the blood levels of catecholamines should be made with reference to indices of sodium balance, such as urinary sodium excretion. (JClin Endocrinol Metab 48: 26, 1978)
consistent pattern. The incidence of elevated blood levels of catecholamines varied from 27-75% in various reports (1, 3,11). On the other hand, others found no differences in blood norepinephrine (NE) among normal and hypertensive subjects (12, 13). Finally, Louis et al. (14) and DeQuattro et al. (11) reported a significant correlation between blood pressure and blood levels of NE, while others did not find such a relationship (15). The reasons for these discrepancies are not clear. It is possible that, as in the case of PRA (16), the state of sodium balance may play an important role in the determination of blood levels of catecholamines. The present study was undertaken to examine the effect of changes in sodium intake on blood levels of catecholamines in normal subjects in an effort to determine a frame of reference for a possible relationship between these two parameters.
Materials and Methods Thirteen normal male subjects, aged 30-53 yr [39.7 ± 2.9 were studied. Before being accepted to the study, they should have fulfilled the following criteria: normal physical examination and normal routine blood chemistry, blood count, urinalysis, creatinine clearance, and normal electrocardiogram (SE)],
26 The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 May 2015. at 08:05 For personal use only. No other uses without permission. . All rights reserved.
27
PLASMA CATECHOLAMINES AND NA INTAKE and chest x-ray. After the nature and purpose of the study were explained, an informed consent was obtained and the subjects were admitted to the Clinical Research Center and remained there for the entire period of the study. They ingested the same diet through the study. It contained constant amounts of protein and provided 10 meq sodium and 80 meq potassium/day. The sodium intake was varied by supplementing salt. They first received 10 meq sodium/day for 7 days, followed by 100 meq/day for 7 days, and finally 200 meq/day during the last 7 days of the study. Only 11 patients were studied with a salt intake of 100 meq/day and 10 patients with 200 meq/day. Twenty-four-hour urine collections were obtained daily throughout the study for measurement of creatinine, sodium, and potassium excretion. It was apparent that the subjects achieved sodium balance by the sixth day of each dietary intake. Therefore, measurements of blood catecholamines were obtained on the seventh day of each of the three periods of the study. On the seventh day, the subjects assumed the recumbent position at 0600 h after emptying their bladders. An angiocath was inserted into a vein at 0700 h while the subjects were still in the supine position and a blood sample was obtained. The subjects then assumed upright posture and remained standing for 20 min, followed by 40 min of ambulation. Blood samples were obtained at 5,10,15, 20, and 60 min after assuming upright posture. Blood pressure measurements were obtained with a standard sphygmomanometer after resting supine for 1 h and after 5 min of upright posture. The pressure at the disappearance of the Korotkoff sounds, phase V, was used as diastolic blood pressure. Each blood pressure recording was the mean of three different readings over a period of 3-4 min. Sodium and potassium were determined by Instrumentation Laboratory flame photometer, and creatinine was measured 1. Sodium excretion, renal function, body weight, and blood pressure during the three periods of various salt intakes
TABLE
Low sodium (n = 13)
Wt
10.5 ± 75.1 ± 114.9 ± 64.8 ±
2.1 6.1 5.8 3.68
Blood pressure Supine systolic Supine diastolic Upright systolic Upright diastolic
111.3 ± ,74.9 ± 110.1 ± 74.6 ±
2.04 1.05 2.65 2.37
UN.V (meq/24 h) UKV (meq/24 h) CCR (ml/min- 1.73 m2)
Medium sodium (n = ll) 101 ± 7.1 73.7 ± 5.6 124 ± 11.6 66.0 ± 3.83° 111.8 ± 73.7 ± 114.1 ± 77.9 ±
2.45 1.15 2.55 1.70
High sodium (n = 10) 196 ± 13.3 70.5 ± 9.3 111 ± 10 66.0 ± 3.81° 111.5 ± 73.8 ± 110.5 ± 74.8 ±
1.69 1.84 3.03 1.31
UNiV, Urinary sodium; UKV, urinary potassium; CCR, endogenous creatinine clearance. Data are presented as the mean ± SE. " P < 0.01 compared to low sodium. Comparisons were made only between subjects who completed all three phases of the study.
with the Technicon autoanalyzer. PRA was assayed in duplicate samples by the RIA of Sealey et al. (17). Plasma NE, epinephrine (Ep), and dopamine (D) concentrations were determined by the radioenzymatic method of Da Prada et al. (18). The sensitivity of this method is 1.0 pg/ml for NE and Ep and 5.0 pg/ml for D. The statistical evaluation of the results was made with paired analysis and Student's t test.
Results The mean values of 24-h urinary excretion of sodium and potassium, creatinine clearance, body weight, and blood pressure during the last day of each of the study periods are given in Table 1. It is evident that urinary sodium excretion on the seventh day of each study period was equal to sodium intake of the respective period. The ingestion of medium or high salt intake resulted in significant increase in body weight. Supine or upright blood pressure was not significantly different with different intakes of salt. Table 2 provides the mean values of plasma catecholamines and PRA for patients while in a supine position with various levels of salt intake. The levels of plasma NE, Ep, D, and PRA were significantly higher during low salt intake than during either medium or high salt intake. It should be emphasized that even the patients who did not have markedly elevated levels of NE on a low salt diet (
Vol. 48, No. 1 Printed in U.S.A.
Effect of Sodium Intake on Plasma Catecholamines in Normal Subjects* MARK S. ROMOFF, GERALD KEUSCHf, VITO M. CAMPESE, MAW-SONG WANG, ROBERT M. FRIEDLER, PETER WEIDMANN, AND SHAUL G. MASSRY Division of Nephrology and Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90033
ABSTRACT. The effect of the state of sodium balance on the activity of the sympathetic nervous system has been evaluated previously by measuring urinary catecholamine excretion. Since urinary catecholamine may be affected by factors such as renal function or renal production of catecholamines, blood catecholamines may provide a better index of the activity of the sympathetic nervous system. The present study was undertaken to evaluate the effect of varying sodium intake on blood catecholamines. Thirteen normal subjects were studied for a period of 3 weeks in a metabolic ward. They received during the first, second, and third week 10, 100, and 200 meq sodium/day, respectively. On the seventh day of each week, when the patients had achieved sodium balance, urinary sodium excretion as well as blood levels of PRA, norepinephrine (NE), epinephrine (Ep), and dopamine (D) were measured in the supine position, at 5, 10, 15, and 20 min of upright posture, and at the end of 40 min of ambulation.
S
EVERAL lines of evidence point toward the possible role of increased activity of the sympathetic nervous system in the genesis of essential hypertension (1-3). Esler et al. found hemodynamic evidence of sympathetic hyperactivity in a group of patients with high renin hypertension (4). However, Mitchell et al. (5) did not find differences in plasma catecholamine levels among hypertensive patients with different levels of PRA. The data on the relationship between urinary or blood catecholamines and essential hypertension are controversial. Some investigators have reported elevated levels of urinary catecholamines in 5-33% of patients (6-9), whereas others have found decreased excretion (10). Measurements of blood levels of catecholamines did not reveal a
Received June 5, 1978. Address all correspondence and requests for reprints to: Shaul G. Massry, M. D., Professor of Medicine, Division of Nephrology, University of Southern California, School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033. * This work was presented before the 10th Annual Meeting of the American Society of Nephrology, Washington DC, November 20-22, 1977. It was supported by grants from the American Heart Association Affiliate of Greater Los Angeles (523), a grant from USPHS Service (GCRC RR-43), and a grant from Hoffman-LaRoche Laboratories, Basel, Switzerland. f Supported by the Swiss National Science Foundation.
The results show that: 1) blood levels of NE, Ep, and D as well as PRA were significantly higher during low sodium intake than during medium or high sodium intake, 2) as in the case of PRA, there was an inverse relationship between the blood levels of NE, Ep, and urinary sodium excretion; 3) upright posture produced a significant increment in the blood levels of NE which was not affected by sodium intake; and 4) the increment in PRA with posture was significantly greater during low sodium intake than with medium high sodium intake. The data demonstrate that: 1) the plasma levels of NE, Ep, and D are affected by the state of sodium balance, particularly during marked sodium depletion; and 2) meaningful interpretation of the significance of the blood levels of catecholamines should be made with reference to indices of sodium balance, such as urinary sodium excretion. (JClin Endocrinol Metab 48: 26, 1978)
consistent pattern. The incidence of elevated blood levels of catecholamines varied from 27-75% in various reports (1, 3,11). On the other hand, others found no differences in blood norepinephrine (NE) among normal and hypertensive subjects (12, 13). Finally, Louis et al. (14) and DeQuattro et al. (11) reported a significant correlation between blood pressure and blood levels of NE, while others did not find such a relationship (15). The reasons for these discrepancies are not clear. It is possible that, as in the case of PRA (16), the state of sodium balance may play an important role in the determination of blood levels of catecholamines. The present study was undertaken to examine the effect of changes in sodium intake on blood levels of catecholamines in normal subjects in an effort to determine a frame of reference for a possible relationship between these two parameters.
Materials and Methods Thirteen normal male subjects, aged 30-53 yr [39.7 ± 2.9 were studied. Before being accepted to the study, they should have fulfilled the following criteria: normal physical examination and normal routine blood chemistry, blood count, urinalysis, creatinine clearance, and normal electrocardiogram (SE)],
26 The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 May 2015. at 08:05 For personal use only. No other uses without permission. . All rights reserved.
27
PLASMA CATECHOLAMINES AND NA INTAKE and chest x-ray. After the nature and purpose of the study were explained, an informed consent was obtained and the subjects were admitted to the Clinical Research Center and remained there for the entire period of the study. They ingested the same diet through the study. It contained constant amounts of protein and provided 10 meq sodium and 80 meq potassium/day. The sodium intake was varied by supplementing salt. They first received 10 meq sodium/day for 7 days, followed by 100 meq/day for 7 days, and finally 200 meq/day during the last 7 days of the study. Only 11 patients were studied with a salt intake of 100 meq/day and 10 patients with 200 meq/day. Twenty-four-hour urine collections were obtained daily throughout the study for measurement of creatinine, sodium, and potassium excretion. It was apparent that the subjects achieved sodium balance by the sixth day of each dietary intake. Therefore, measurements of blood catecholamines were obtained on the seventh day of each of the three periods of the study. On the seventh day, the subjects assumed the recumbent position at 0600 h after emptying their bladders. An angiocath was inserted into a vein at 0700 h while the subjects were still in the supine position and a blood sample was obtained. The subjects then assumed upright posture and remained standing for 20 min, followed by 40 min of ambulation. Blood samples were obtained at 5,10,15, 20, and 60 min after assuming upright posture. Blood pressure measurements were obtained with a standard sphygmomanometer after resting supine for 1 h and after 5 min of upright posture. The pressure at the disappearance of the Korotkoff sounds, phase V, was used as diastolic blood pressure. Each blood pressure recording was the mean of three different readings over a period of 3-4 min. Sodium and potassium were determined by Instrumentation Laboratory flame photometer, and creatinine was measured 1. Sodium excretion, renal function, body weight, and blood pressure during the three periods of various salt intakes
TABLE
Low sodium (n = 13)
Wt
10.5 ± 75.1 ± 114.9 ± 64.8 ±
2.1 6.1 5.8 3.68
Blood pressure Supine systolic Supine diastolic Upright systolic Upright diastolic
111.3 ± ,74.9 ± 110.1 ± 74.6 ±
2.04 1.05 2.65 2.37
UN.V (meq/24 h) UKV (meq/24 h) CCR (ml/min- 1.73 m2)
Medium sodium (n = ll) 101 ± 7.1 73.7 ± 5.6 124 ± 11.6 66.0 ± 3.83° 111.8 ± 73.7 ± 114.1 ± 77.9 ±
2.45 1.15 2.55 1.70
High sodium (n = 10) 196 ± 13.3 70.5 ± 9.3 111 ± 10 66.0 ± 3.81° 111.5 ± 73.8 ± 110.5 ± 74.8 ±
1.69 1.84 3.03 1.31
UNiV, Urinary sodium; UKV, urinary potassium; CCR, endogenous creatinine clearance. Data are presented as the mean ± SE. " P < 0.01 compared to low sodium. Comparisons were made only between subjects who completed all three phases of the study.
with the Technicon autoanalyzer. PRA was assayed in duplicate samples by the RIA of Sealey et al. (17). Plasma NE, epinephrine (Ep), and dopamine (D) concentrations were determined by the radioenzymatic method of Da Prada et al. (18). The sensitivity of this method is 1.0 pg/ml for NE and Ep and 5.0 pg/ml for D. The statistical evaluation of the results was made with paired analysis and Student's t test.
Results The mean values of 24-h urinary excretion of sodium and potassium, creatinine clearance, body weight, and blood pressure during the last day of each of the study periods are given in Table 1. It is evident that urinary sodium excretion on the seventh day of each study period was equal to sodium intake of the respective period. The ingestion of medium or high salt intake resulted in significant increase in body weight. Supine or upright blood pressure was not significantly different with different intakes of salt. Table 2 provides the mean values of plasma catecholamines and PRA for patients while in a supine position with various levels of salt intake. The levels of plasma NE, Ep, D, and PRA were significantly higher during low salt intake than during either medium or high salt intake. It should be emphasized that even the patients who did not have markedly elevated levels of NE on a low salt diet (
