Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Baxter, John D.; Schambelan, Morris; Matulich, Daniel T.; Spindler, Benjamin; Taylor, Addison A.; Bartter, Frederic C.

doi:10.1172/jci108504

Cited by 53 publications

(11 citation statements)

References 49 publications

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“…The affinities as determined by competition for other steroids relative to aldosterone (100%) are: 11-deoxycortisol, 48%; cortisol, 1.5%; 18-OH-DOC,(1) 1.2%. These values are similar to those in the rat (Baxter et al, 1976). No ( I ) Abbreviations: I8-OH-DOC, 18-hydroxydeoxycorticosterone; 16B-OH-DHEA.…”

Section: Resultssupporting

confidence: 83%

“…glucocorticoids; Ballard, Carter, Graham & Baxter, 1974), some differences in steroid potencies and in receptor binding between rat and man have been noted. To further explore this point, we examined binding by receptors in human kidney samples obtained after therapeutic nephrectomy (Matulich, Spindler, Schambelan & Baxter, 1976). The apparent affinity of ['Hlaldosterone for these receptors was 0.5 nmol/l.…”

Section: Resultsmentioning

confidence: 99%

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Role of Steroids in Hypertension: Evaluation of Plasma Mineralocorticoid Activity with Aldosterone Receptors

et al. 1976

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1. A competitive 'mineralocorticoid' receptorbinding technique has been used to study plasma 'mineralocorticoid' activity in normal and hypertensive states. The binding reaction mixture contains the competitor steroids . in undiluted plasma,[3H]aldosterone and rat kidney slices. Thus plasma binding and receptor occupancy can be simultaneously considered.2. Competitor activities relative to that of aldoterone (100%) were: deoxycorticosterone (DOC), 16% ; cortisol, 0.4%; 18-hydroxydeoxycorticosterone (1 8-OH-DOC), 0.1 % ; 16B-OH-dehydroepiandrosterone and 16-oxo-androstenedioI, inactive. (Binding characteristics for aldosterone and the other steroids tested with the rat receptor were found to be similar to those with receptors in slices from human kidney, obtained at operation.) These steroids and the spironolactone SC14266 were less active in plasma than in buffer, suggesting that they bind significantly to plasma and that this reduces their capacity to occupy the receptors.3. These competition data also suggest that at normal and even mildly elevated concentrations, cortisol does, but DOC and 18-OH-DOC do not, contribute significantly to the plasma mineralocorticoid activity. Competitor activity in plasma samples taken at 12.00 hours from normal subjects (upright) was greater than that in those taken at 08.00 hours (supine). This physiological change, corresponding to an increase in aldosterone, was detected even though there was an associated decrease in plasma cortisol. Competitor activity in Correspondence: Dr John D. Baxter, Metabolic Research Unit, 1143 HSW, University of California, San Francisco, CA 94143, U.S.A.plasma from patients with primary aldosteronism was markedly elevated as compared with that of normal subjects. However, an increase in plasma steroids which bind to the mineralocorticoid receptor was not detected in plasma from patients with 'low-renin essential hypertension'.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Role of Steroids in Hypertension: Evaluation of Plasma Mineralocorticoid Activity with Aldosterone Receptors

et al. 1976

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“…2 were subjected to computerized analysis by the nonlinear multiparameter LI-GAND program developed by Munson and Rodbard (17). Best fit to the data was obtained by a model involving two classes of (31). Taken together, these data indicate that the concentrations of maleyl-albumin inducing chemotaxis correlate with the binding of the ligand to the second, lower affinity site present on human monocytes (Fig.…”

Section: Resultsmentioning

confidence: 83%

Receptor recognition of maleyl-albumin induces chemotaxis in human monocytes.

Rasmussen¹,

Fogelman²

1986

J. Clin. Invest.

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We demonstrate here that the exceptionally active maleylalbumin receptor of human monocytes functions in vitro as a chemoattractant receptor. Chemotaxis of human monocytes occurs at an effective median dose of 34 MM maleyl-albumin, a concentration representing 1% of the total albumin in the adult human. Computerized analyses by LIGAND of the saturable binding of maleyl-albumin to human monocytes reveal two classes of binding sites, described by dissociation constants of 37 nM and 5.3 MAM with maximal binding of 1.6 and 23 pmol maleylalbumin/mg cellular protein, respectively. Chemotaxis of human monocytes thus occurs at concentrations of maleyl-albumin promoting binding to the lower-affinity sites.We propose that conformational isomers of albumin that are chemotactic may form in vivo and that albumin, in addition to receptor-independent plasma transport functions, may also play an important role in the receptor-mediated recruitment and accumulation of phagocytic cells at sites of inflammation and injury.

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“…The levels achieved in this study, however, are probably high enough to cause near maximal mineralocorticoid receptor occupancy, leading to marked and rapid sodium retention. 14 The consistent decrease in urinary potassium excretion following implantation is surprising. Mineralocorticoids have potent kaliuretic effects in rat, dog, and man, 2> "• 18> " and renal potassium loss has been used as a marker of mineralocorticoid activity in bioassay systems.…”

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confidence: 99%

Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs.

Grekin

Terris²,

Bohr³

1980

Hypertension

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SUMMARY Balances of sodium, potassium, and water were studied in the growing male pig as hypertension developed in response to subcutaneous implantation of deoxycorticosterone acetate (DOCA). Serum sodium, potassium, deoxycorticosterone (DOC), aldosterone, and plasma renln actirity (PRA) were determined. These variables were observed in a total of 10 experimental and nine control pigs. All animals were uninephrectomized and fed a diet of Purina Pig Chow and tap water ad libitum. No salt was added to the food or water. Serum DOC levels rose dramatically on the day of the implantation, then gradually declined but remained approximately 10 times greater than control levels 40 days after Implant.Plasma renln activity was suppressed rapidly and completely, whereas aldosterone fell only slowly to about half its control value. Sodium retention was maximum during the first 24 hours. Thereafter an "escape" process became operative, causing sodium balance to return to normal after the third day, at which time the major rise in arterial pressure occurred. A marked increase in water turnover (intake and output) also began after the third day and persisted throughout the experimental period. Water balance remained normal during this period of increased turnover. Hypokalemia developed in the absence of kaliuresis, suggesting that potassium moved Into the cells. Except for the potassium retention, these changes parallel the abnormalities seen in other states of mineralocorticoid excess. • * Despite the large number of studies performed upon these experimental models, the pathogenesis of hypertension remains controversial.We have developed an animal model for mineralocorticoid hypertension using deoxycorticosterone acetate (DOCA) implantation in pigs, which offers several advantages for the study of hypertension. These include the rapid and highly reproducible elevation in blood pressure and the relatively large size of the animal, which allows for accurate hemodynamic measurements." In this report we describe the electrolyte and hormonal changes seen during the development of DOCA hypertension in pigs.

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Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Cited by 53 publications

References 49 publications

Role of Steroids in Hypertension: Evaluation of Plasma Mineralocorticoid Activity with Aldosterone Receptors

Role of Steroids in Hypertension: Evaluation of Plasma Mineralocorticoid Activity with Aldosterone Receptors

Receptor recognition of maleyl-albumin induces chemotaxis in human monocytes.

Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs.

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