Myocardial fibrosis in the rat with mineralocorticoid excess prevention of scarring by amiloride

Scott E. Campbell, Joseph S. Janicki, Beatrix B. Matsubara, Karl Weber

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

In both humans and experimental animals, mineralocorticoid (MC)-induced hypertension is associated with myocardial fibrosis. We have shown that this fibrous tissue response includes a reactive interstitial fibrosis not initiated by parenchymal cell loss, and a reparative fibrosis or scarring, occurring in response to cardiac myocyte necrosis. The reactive fibrosis is thought to be related to MC excess, while cell loss and microscopic scarring may be secondary to enhanced potassium excretion or a cytotoxic effect of aldosterone. This histologic study was undertaken to determine whether or not the potassium sparing diuretic amiloride would be effective in preventing the appearance of either form of fibrosis. Uninephrectomized male Sprague Daw- ley rats received either aldosterone (AL; 0.75 ¡ig/h), amiloride (AMC; 1 mg/kg/day), aldosterone + amiloride (ALAM), or vehicle (ALC) alone via subcutaneous osmotic minipumps for 8 weeks. All rats received 1% NaCl in their drinking water. Hearts were recovered, immersion-fixed, and tissue sec-tions from both left and right ventricles stained with the collagen specific stain Sirius Red F3BA were morphometrically analyzed. The interstitial collagen volume fraction was elevated in AL and ALAM groups compared to ALC and AMC, but did not differ between AL and ALAM. Microscopic scarring, found in both ventricles, was evident in AL animals, but was not found in the ALAM, AMC, or ALC groups. These data suggest that chronic elevations in plasma aldosterone, relative to dietary sodium intake, do not have a direct cytotoxic effect on cardiac myocytes, but they are associated with a reactive interstitial fibrosis. Myocyte necrosis in hyperaldosteronism, as gauged by the appearance of scarring, is likely a result of enhanced potassium excretion and can be prevented by amiloride.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalAmerican journal of hypertension
Volume6
Issue number6
DOIs
StatePublished - Jan 1 1993

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Mineralocorticoids
Amiloride
Aldosterone
Cicatrix
Fibrosis
Cardiac Myocytes
Heart Ventricles
Potassium
Necrosis
Collagen
Potassium Sparing Diuretics
Dietary Sodium
Hyperaldosteronism
Immersion
Drinking Water
Muscle Cells
Coloring Agents
Hypertension

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Myocardial fibrosis in the rat with mineralocorticoid excess prevention of scarring by amiloride. / Campbell, Scott E.; Janicki, Joseph S.; Matsubara, Beatrix B.; Weber, Karl.

In: American journal of hypertension, Vol. 6, No. 6, 01.01.1993, p. 487-495.

Research output: Contribution to journalArticle

Campbell, Scott E. ; Janicki, Joseph S. ; Matsubara, Beatrix B. ; Weber, Karl. / Myocardial fibrosis in the rat with mineralocorticoid excess prevention of scarring by amiloride. In: American journal of hypertension. 1993 ; Vol. 6, No. 6. pp. 487-495.
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