Mineralocorticoids, hypertension, and cardiac fibrosis

Morag Young, Meryl Fullerton, Rodney Dilley, John Funder

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 μg/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid- antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic and tissue responses were compared with a non-steroid-treated control group. Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC x 1.8-, RU486 x 1.6-, B x 1.3-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 vs all other groups); RU486 raised levels 1.4-fold vs control, but neither Aldo nor B significantly affected perivascular collagen. These data are consistent with interstitial cardiac fibrosis reflecting type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy.

Original languageEnglish
Pages (from-to)2578-2583
Number of pages6
JournalJournal of Clinical Investigation
Volume93
Issue number6
DOIs
Publication statusPublished - 1 Jan 1994
Externally publishedYes

Keywords

  • aldosterone
  • deoxycorticosterone
  • interstitial fibrosis
  • perivascular fibrosis
  • RU486

Cite this

Young, Morag ; Fullerton, Meryl ; Dilley, Rodney ; Funder, John. / Mineralocorticoids, hypertension, and cardiac fibrosis. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 6. pp. 2578-2583.
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Mineralocorticoids, hypertension, and cardiac fibrosis. / Young, Morag; Fullerton, Meryl; Dilley, Rodney; Funder, John.

In: Journal of Clinical Investigation, Vol. 93, No. 6, 01.01.1994, p. 2578-2583.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Young, Morag

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AB - Uninephrectomized rats drinking 1% sodium chloride were given aldosterone (Aldo, 0.75 μg/h, subcutaneous [s.c.] infusion), deoxycorticosterone (DOC, 20 mg/wk, s.c.), corticosterone (B, 2 mg/d, s.c.), or the antiglucocorticoid- antiprogestin RU486 (2 mg/d, s.c.) for 8 wk, and hemodynamic and tissue responses were compared with a non-steroid-treated control group. Aldo and DOC markedly increased systolic BP and caused considerable (40-50%) cardiac hypertrophy; B and RU486 caused neither hypertension nor cardiac hypertrophy. Measurements of ventricular cross-sectional areas showed hypertrophy due to an increase in mass of the left ventricle only. Cardiac hydroxyproline concentration was increased considerably by Aldo and DOC, to a lesser degree by RU486, and not by B. Aldo markedly elevated left ventricular interstitial collagen (2.5-fold vs control, P < 0.01 vs all groups); other steroid treatments also increased interstitial collagen over control (DOC x 1.8-, RU486 x 1.6-, B x 1.3-fold), with identical responses for right and left ventricles (r = 0.94). A different pattern of perivascular fibrosis was noted; DOC elevated perivascular collagen (2.1-fold vs control, P < 0.01 vs all other groups); RU486 raised levels 1.4-fold vs control, but neither Aldo nor B significantly affected perivascular collagen. These data are consistent with interstitial cardiac fibrosis reflecting type I (mineralocorticoid) receptor occupancy by administered Aldo or DOC, or by elevated endogenous B after type II (glucocorticoid) receptor blockade after RU486 administration; perivascular fibrosis may reflect a composite response after type I receptor agonist/type II glucocorticoid receptor antagonist occupancy.

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