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Cardiac and vascular fibrosis and hypertrophy in aldosterone-infused rats: role of endothelin-1.

Abstract
Increased endothelin-1 (ET-1) or aldosterone may be associated with promotion of cardiovascular hypertrophy and fibrosis. We evaluated whether the selective ETA receptor-antagonist BMS 182874 (BMS) prevents cardiac and vascular collagen deposition and hypertrophy in aldosterone-infused rats. Rats received subcutaneous aldosterone (0.75 microg/h) and 1% sodium chloride in drinking water +/- BMS (40 mg/kg per day in food) for 6 weeks. Heart and aorta were cross-sectioned and stained with Sirius red. Heart weight did not change with either aldosterone infusion or BMS treatment. Cardiac and aortic interstitial and perivascular collagen were quantified with videomorphometry. Aortic collagen and media cross-sectional area were significantly increased 3.5-fold (P < .01) and 1.13-fold (P < .05), respectively, with aldosterone infusion and decreased in BMS-treated rats (P < .05, P < .001, respectively). Aldosterone infusion increased interstitial and perivascular collagen in the left (1.6- and 2.7-fold, P < .05 and P < .01, respectively) and right ventricle (1.5- and 1.7-fold, P > .05 and P < .05, respectively). BMS prevented collagen deposition except for interstitial collagen in the right ventricle. Cardiac and aortic fibrosis were significantly increased in aldosterone-infused hypertensive rats. The ETA receptor antagonist prevented cardiac and aortic collagen deposition and aortic hypertrophy. This suggests a role for ET-1 in fibrosis of heart and large vessels in conditions associated with mineralocorticoid excess.
AuthorsJeong Bae Park, Ernesto L Schiffrin
JournalAmerican journal of hypertension (Am J Hypertens) Vol. 15 Issue 2 Pt 1 Pg. 164-9 (Feb 2002) ISSN: 0895-7061 [Print] United States
PMID11863252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antihypertensive Agents
  • Dansyl Compounds
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Receptor, Endothelin A
  • 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide
  • Aldosterone
  • Collagen
Topics
  • Aldosterone
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Aorta (drug effects, pathology)
  • Aortic Diseases (chemically induced, pathology, physiopathology)
  • Blood Pressure
  • Body Weight
  • Cardiomyopathies (chemically induced, pathology, physiopathology)
  • Collagen (metabolism)
  • Dansyl Compounds (pharmacology)
  • Endothelin Receptor Antagonists
  • Endothelin-1 (metabolism)
  • Fibrosis
  • Heart (drug effects)
  • Hypertrophy
  • Male
  • Myocardium (metabolism, pathology)
  • Organ Size
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A

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