The renin-angiotensin-aldosterone system in experimental mineralocorticoid-salt-induced cardiac fibrosis

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Aldosterone infused for 8 wk to uninephrectomized rats drinking saline solution causes cardiac fibrosis. To investigate the renin-angiotensin system (RAS) in this process, we blocked angiotensin-converting enzyme with perindopril and angiotensin I receptors with losartan. To distinguish aldosterone effects via 11β-hydroxysteroid dehydrogenase type 2-protected epithelial mineralocorticoid receptors (MR) and unprotected cardiac MR, we compared preferential exclusion of aldosterone from unprotected MR by corticosterone and generalized MR blockade by K1 canrenoate. Perindopril and losartan modestly lowered blood pressure (BP); neither affected cardiac hypertrophy, hydroxyproline content, or perivascular fibrosis, and both slightly attenuated aldosterone effects on interstitial collagen. Corticosterone did not affect cardiac hypertrophy but halved aldosterone- induced elevation of BP and collagen levels. Canrenoate halved the increase in BP and hypertrophy and completely reversed aldosterone-induced increase in cardiac collagen. We conclude that 1) the circulating and tissue RAS are, at most, minor contributors to cardiac fibrosis in aldosterone-infused, salt- loaded rats; and 2) both BP elevation and increased cardiac collagen appear to reflect aldosterone occupancy of unprotected MR, consistent with a direct cardiac effect of aldosterone on fibrosis.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 34-5
Publication statusPublished - Nov 1996
Externally publishedYes


  • losartan
  • mineralocorticoid receptors
  • perindopril
  • potassium canrenoate

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