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.