Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride.
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 Dawley rats received either aldosterone (AL; 0.75 microgram/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 sections 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
S E
SE
Department of Internal Medicine, University of Missouri, Columbia 65212.
Janicki
J S
JS
Matsubara
B B
BB
Weber
K T
KT
D000450:Aldosterone / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000584:Amiloride / Q000627:therapeutic use*; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D002921:Cicatrix / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000032:analysis / Q000648:ultrastructure; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005355:Fibrosis / Q000209:etiology; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology; D006984:Hypertrophy / Q000473:pathology; D008297:Male; D008901:Mineralocorticoids / Q000009:adverse effects*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D008901:Mineralocorticoids; D000450:Aldosterone; D000584:Amiloride; D003094:Collagen