Distribution, conjugation, and excretion of labeled aldosterone in congestive heart failure and in controls with normal  circulation: development and testing of a model with an analog computer.

Cheville, R.A.; Luetscher, John A.; Hancock, Elizabeth; Dowdy, A. J.; Nokes, G. W.

doi:10.1172/jci105437

Cited by 49 publications

(16 citation statements)

References 18 publications

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“…The proportion of the oral compared with the intravenous dose excreted as the aldosterone released from the acid labile conjugate is similar (about 75%) for the young and elderly subjects (Table III). As the acid labile conjugate is the major extrahepatic route of metabolism (16,17), this indicates that the amount of such metabolism is not altered appreciably in elderly subjects (12). It therefore appears that some of the lowering of the MCR must be due to decreased hepatic blood flow.…”

Section: Discussionmentioning

confidence: 99%

“…For subjects with minimal and marked cardiac dysfunction (7) (14,17). The observation of the markedly decreased secretion rate of aldosterone in elderly subjects emphasizes the need, whatever the mechanism of the effect, for the use of control subjects in the appropriate age group particularly in the studies of the secretion of aldosterone in heart failure and hypertension.…”

Section: Discussionmentioning

confidence: 99%

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The Metabolism and Secretion of Aldosterone in Elderly Subjects*

Flood¹,

Gherondache²,

Pincus³

et al. 1967

J. Clin. Invest.

115

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Summary. The secretion rates [34 + 6 (SE) ug per day, 9 subjects] and metabolic clearance rates (MCR) [1,288 ± 120 (SE) L of plasma per day, 9 subjects] of aldosterone in elderly subjects are significantly lower than those of young subjects [77 + 7 (SE) Mug per day and 1,631 + 106 (SE) L per day, respectively]. There is a correlation of the MCR and secretion rate values (p = 0.02), but the calculated plasma concentrations (secretion rate/ MCR) are also significantly low in the elderly subjects [2.6 + 0.3 (SE) compared with concentrations in the plasma from young subjects of 4.7 + 0.6 (SE) ug per 100 ml plasma].The urinary excretion of radioactivity from oral and intravenously administered labeled aldosterone as aldosterone in the neutral extract, as aldosterone released by acid hydrolysis, and as tetrahydroaldosterone released by incubation with /-glucuronidase is generally similar for young and elderly subjects except that a larger portion of the oral compared with the intravenous dose is excreted as free aldosterone in the elderly subjects, indicating that the splanchnic extraction is reduced. The calculated splanchnic blood flow (assuming no alteration in extrasplanchnic metabolism) is also slightly lowered.Therefore, as in patients with mild cardiac dysfunction, the lowered MCR of elderly subjects is due to both reduced splanchnic extraction and blood flow. However, unlike the heart failure patients, in the elderly subjects the plasma concentration of aldosterone is also reduced.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Metabolism and Secretion of Aldosterone in Elderly Subjects*

Flood¹,

Gherondache²,

Pincus³

et al. 1967

J. Clin. Invest.

115

View full text Add to dashboard Cite

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“…Also, after oral administration of the natural hormone, only 8%o is released by mild acid hydrolysis as aldosterone (corrected for recovery of the released aldosterone), and after intravenous injection, the corresponding quantity is 10% (2,5,10). The difference in excretion of aldosterone in the acid extract after oral compared to intravenous injection of aldosterone has been postulated as being due to high hepatic extraction of aldosterone with some extrahepatic conversion of the intravenous aldosterone to the acid-labile conjugate (2,14).…”

Section: Discussionmentioning

confidence: 99%

“…It would then be expected that the decreased rate of metabolism of the orally administered 17-isoaldosterone in the liver, due to lack of reduction of the A-ring, would lead to lowered hepatic extraction. Some of the orally administered steroid would then reach the kidney, which can form the acid-labile conjugate ( 14). The proportion of 17-isoaldosterone metabolized to the conjugate would then be expected to be much higher than that of oral aldosterone.…”

Section: Discussionmentioning

confidence: 99%

“…We have no explanation for this discrepancy. Cheville and co-workers (14), from analysis of renal venous blood and urinary excretion of conjugate in control subjects and patients with early heart failure, concluded that 61% (with confidence limits ± 20%o) of the acid-labile conjugate is formed in the kidney. From the isotopic ratios obtained in the present studies for aldosterone from the 18-glucuronide (0.75 ± 0.04) and tetrahydroaldosterone (1.14 ± 0.04), the proportion of the total 18-glucuronide formed in the splanchnic circulation produced from secreted hormone can be calculated (Equation 9) as 0.66 + 0.05 or 34 ± 5% of the total conjugate is formed from secreted hormone extrasplanchnically.…”

Section: Discussionmentioning

confidence: 99%

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A Comparison of the Metabolism of Radioactive 17-Isoaldosterone and Aldosterone Administered Intravenously and Orally to Normal Human Subjects*

Flood¹,

Pincus²,

Tait³

et al. 1967

J. Clin. Invest.

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Summary. After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 + 0.4 (SE) and 5.4 ± 0.5 (SE) %, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 + 5 (SE) and 39 + 4 (SE) %, respectively, was recovered as tetrahydroaldosterone after incubation with 1e3-glucuronidase.After intravenous and oral administration of 17-isoaldosterone-4-"4C to a similar group of subjects, 35 ± 3 (SE) and 53 ± 4 (SE) %, respectively, of the dose was recovered as 17-isoaldosterone released by acid and less than 5% as total metabolites after incubation with fl-glucuronidase. No detectable radioactivity (< 0.5%) could be recovered as tetrahydroaldosterone or as a compound with the expected chromatographic properties of tetrahydro-17-isoaldosterone. The total radioactivity in the neutral extracts was also relatively small (< 2%) after administration of either labeled aldosterone or 17-isoaldosterone. These results indicated that, due to lack of A-ring reduction of the molecule and the consequent slowing of hepatic clearance, 17-isoaldosterone is converted to an acid-labile conjugate (presumably 17-isoaldosterone 18-glucuronide) as the major metabolite. 17-Isoaldosterone was not secreted or converted to aldosterone to any significant extent in the normal subjects investigated.

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