Aldosterone Metabolic Clearance is Normal in Low-Renin Essential Hypertension RONALD D. BROWN Department of Medicine, Baylor College of Medicine, Houston, Texas 77025 hours. These values were not significantly different from those of normal subjects. Although aldosterone secretion rates in both groups of hypertensive patients were within the normal range, patients with low-renin essential hypertension, under the conditions of this study, had significantly higher secretion rates than patients with normal-renin essential hypertension. We have concluded that the maintenance of plasma aldosterone in low-renin essential hypertension reflects sustained aldosterone secretion despite suppression of plasma renin activity, rather than reduced aldosterone metabolism. The maintenance of normal aldosterone secretion in low-renin essential hypertension appears to be inappropriate and is not explained by alterations of known regulatory mechanisms. (J Clin Endocrinol Metab 42: 661, 1976)
ABSTRACT. The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritiumlabeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 ± 69 (mean ± SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 ± 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 ± 66 liters/24
D
URING the past few years substantial evidence has accumulated implicating the adrenal cortex in the pathogenesis of low-renin essential hypertension. It has been reported that patients with this syndrome show amelioration of their hypertension in response to aminoglutethimide, an inhibitor of adrenal steroidogenesis (1), to spironolactone, a mineralocorticoid antagonist (2-4), and to adrenalectomy (5,6). These patients usually have nonnal urinary aldosterone excretion (2-4) or secretion rates (1), although in a few patients urinary aldosterone is subnormal. The majority of these patients fail to show normal suppression of aldosterone excretion when administered a diet high in sodium content (7). Recently, it was reported that ambulatory lowrenin essential hypertension patients have nonnal but "inappropriately high" plasma
aldosterone levels when ingesting a high sodium diet (8). In the same study, it was shown that following prolonged recumbency, these patients had plasma aldosterone levels that were significantly elevated compared with levels in normal recumbent subjects. These reports of normal or elevated plasma aldosterone levels in patients whose aldosterone excretion and production rates were nonnal or low suggested to us there might be an abnormality of aldosterone metabolic clearance in the syndrome of lowrenin essential hypertension. Altered aldosterone metabolism has previously been reported in some patients with essential hypertension (9,10); however, patients in those studies were not clearly categorized into low-renin and normal-renin subsets. Materials and Methods
Received July 14, 1975. Supported in part by Baylor Clinical Research Center Grant RR 00 134. Presented in part at the meeting of the American Federation for Clinical Research, New Orleans, 1975. Address reprint requests to: Dr. R. D. Brown, Mayo Clinic, Rochester, Minnesota 55901.
Subjects. Nonnal subjects and hypertensive patients were studied at the Clinical Research Center of the Baylor College of Medicine. Informed consent was obtained from all participants. Patients with accelerated or malignant hypertension, congestive heart failure, azotemia, 661
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662
JCE & M • 1976 Vol 42 • No 4
BROWN
or hepatic dysfunction were excluded. None of the patients was receiving oral contraceptives, and all denied eating licorice. All had normal urinary 17-hydroxycorticosteroids, 17-ketosteroids, VMA, and rapid sequence intravenous pyelograms. Some patients had renal arteriograms, all of which were normal. The clinical data of the normal subjects and patients studied are summarized in Table 1. Medications were discontinued at least 7 days prior to admission to the Clinical Research Center. The aldosterone production and clearance studies were begun at least two days after the patients came into balance, ingesting diets providing 120 mEq sodium and 70 mEq potassium daily. All subjects were recumbent for at least 8 hours prior to obtaining blood for recumbent plasma renin activity and plasma aldosterone at 8 AM. They then were ambulatory for a 3 hour period from 8 AM to 11 AM, at the end of which time blood was obtained for upright plasma renin activity and plasma aldosterone. Aldosterone secretion rates were measured while the patient was at ad lib activity. The infusions of tritium-labeled aldosterone for determining aldosterone metabolic clearance were begun between 8-9 AM, after the patients and subjects had been recumbent for at least 8 hours. They remained recumbent throughout the clearance study. After all studies were completed, the patients were classified as to whether they had low-renin (plasma renin activity
ABSTRACT. The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritiumlabeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 ± 69 (mean ± SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 ± 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 ± 66 liters/24
D
URING the past few years substantial evidence has accumulated implicating the adrenal cortex in the pathogenesis of low-renin essential hypertension. It has been reported that patients with this syndrome show amelioration of their hypertension in response to aminoglutethimide, an inhibitor of adrenal steroidogenesis (1), to spironolactone, a mineralocorticoid antagonist (2-4), and to adrenalectomy (5,6). These patients usually have nonnal urinary aldosterone excretion (2-4) or secretion rates (1), although in a few patients urinary aldosterone is subnormal. The majority of these patients fail to show normal suppression of aldosterone excretion when administered a diet high in sodium content (7). Recently, it was reported that ambulatory lowrenin essential hypertension patients have nonnal but "inappropriately high" plasma
aldosterone levels when ingesting a high sodium diet (8). In the same study, it was shown that following prolonged recumbency, these patients had plasma aldosterone levels that were significantly elevated compared with levels in normal recumbent subjects. These reports of normal or elevated plasma aldosterone levels in patients whose aldosterone excretion and production rates were nonnal or low suggested to us there might be an abnormality of aldosterone metabolic clearance in the syndrome of lowrenin essential hypertension. Altered aldosterone metabolism has previously been reported in some patients with essential hypertension (9,10); however, patients in those studies were not clearly categorized into low-renin and normal-renin subsets. Materials and Methods
Received July 14, 1975. Supported in part by Baylor Clinical Research Center Grant RR 00 134. Presented in part at the meeting of the American Federation for Clinical Research, New Orleans, 1975. Address reprint requests to: Dr. R. D. Brown, Mayo Clinic, Rochester, Minnesota 55901.
Subjects. Nonnal subjects and hypertensive patients were studied at the Clinical Research Center of the Baylor College of Medicine. Informed consent was obtained from all participants. Patients with accelerated or malignant hypertension, congestive heart failure, azotemia, 661
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 21 November 2015. at 11:50 For personal use only. No other uses without permission. . All rights reserved.
662
JCE & M • 1976 Vol 42 • No 4
BROWN
or hepatic dysfunction were excluded. None of the patients was receiving oral contraceptives, and all denied eating licorice. All had normal urinary 17-hydroxycorticosteroids, 17-ketosteroids, VMA, and rapid sequence intravenous pyelograms. Some patients had renal arteriograms, all of which were normal. The clinical data of the normal subjects and patients studied are summarized in Table 1. Medications were discontinued at least 7 days prior to admission to the Clinical Research Center. The aldosterone production and clearance studies were begun at least two days after the patients came into balance, ingesting diets providing 120 mEq sodium and 70 mEq potassium daily. All subjects were recumbent for at least 8 hours prior to obtaining blood for recumbent plasma renin activity and plasma aldosterone at 8 AM. They then were ambulatory for a 3 hour period from 8 AM to 11 AM, at the end of which time blood was obtained for upright plasma renin activity and plasma aldosterone. Aldosterone secretion rates were measured while the patient was at ad lib activity. The infusions of tritium-labeled aldosterone for determining aldosterone metabolic clearance were begun between 8-9 AM, after the patients and subjects had been recumbent for at least 8 hours. They remained recumbent throughout the clearance study. After all studies were completed, the patients were classified as to whether they had low-renin (plasma renin activity
