Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure*

Camargo, C. A.; Dowdy, A. J.; Hancock, Elizabeth; Luetscher, John A.

doi:10.1172/jci105149

Cited by 58 publications

(23 citation statements)

References 24 publications

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“…Importantly, these considerations seem also to apply to endogenously produced substances eliminated by the liver. Thus, the clearances of both aldosterone (15) and cortisol (16) have been shown to be flow-dependent.…”

Section: Discussionmentioning

confidence: 99%

Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

Branch¹,

Shand²,

Wilkinson³

et al. 1974

J. Clin. Invest.

132

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A B S T R A C T The effects of phenobarbital treatment for 12 days on the regional distribution of blood flow and on the disposition of two model drugs, antipyrine and d-propranolol, have been determined in six unanesthetized rhesus monkeys. Phenobarbital significantly increased total hepatic blood flow from 179±15 to 239± 27 ml/min. Liver weight was increased to a similar degree (34%) in phenobarbital-treated animals as compared to control monkeys. The clearance of both antipyrine and d-propranolol was increased and the halflife decreased significantly by phenobarbital. Analysis of the data by a perfusion-limited pharmacokinetic model showed that the changes in antipyrine clearance were due almost entirely to enzyme induction. On the other hand, with d-propranolol, the increase in liver blood flow contributed as much to the enhanced clearance as did the stimulation of drug metabolism. The mechanism by which phenobarbital produces the frequently observed increase in drug clearance, therefore, depends upon the initial clearance value of the drug. For low clearance drugs like antipyrine, clearance changes occur largely as a result of enzyme induction. With higher clearance drugs, the effects of increased hepatic blood flow become

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Section: Discussionmentioning

confidence: 99%

Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

Branch¹,

Shand²,

Wilkinson³

et al. 1974

J. Clin. Invest.

132

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“…The decreased secretion rate could be due to a lowering of excretion of sodium because of reduced renal blood flow (15) (or some other factor not involving aldosterone) as the primary event. However, in normal subjects and patients with congestive heart failure similar alterations in renal hemodynamics are accompanied by normal or increased secretion of aldosterone, which is not always due to the dietary regime (14). It remains to be seen whether the production of the stimulatory substance or the response of the adrenal to the stimulus is reduced in the elderly subjects.…”

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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“…The high level of PRA was also observed. Not only the reduction of metabolic clearance rate of aldosterone (Tait et al, 1965;Camargo et al, 1965) but also the high level of PRA would result in the raised concentration of PA in this case. Spironolactone might also induce the hyperaldosteronism through the renin angiotensin system in this patient as indicated by Nicholls et al (1976b).…”

Section: Discussionmentioning

confidence: 88%

The diurnal rhythm of plasma aldosterone and plasma renin activity in patients with congestive heart failure.

et al. 1977

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Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure*

Cited by 58 publications

References 24 publications

Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

The Metabolism and Secretion of Aldosterone in Elderly Subjects*

The diurnal rhythm of plasma aldosterone and plasma renin activity in patients with congestive heart failure.

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