Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries

Background-Coronary artery angioplasty triggers healing that causes constri ctive remodeling. Because collagen accumulation correlates with constrictiv e remodeling and aldosterone has been implicated in collagen accumulation, we examined how aldosterone and the mineralocorticoid receptor antagonists spironolactone and eplerenone affect remodeling and collagen in porcine cor onary and iliac arteries after angioplasty. Methods and Results-Twenty-four pigs were allocated into 4 treatment groups : oral eplerenone (100 mg/d), oral spironolactone (200 mg/d), subcutaneous aldosterone (400 mug/d), or no treatment. Twenty-eight days after angioplas ty of the coronary arteries, eplerenone increased total vessel area by 30% (P<0.05) and luminal area by nearly 60% (P<0.05) compared with the no-treat ment group, without affecting neointima size. These effects were accompanie d by a 65% reduction in neointimal and medial collagen density (both P<0.05 ). Spironolactone was less effective, and aldosterone tended to exert oppos ite effects on coronary artery structure after angioplasty. These effects w ere not observed in angioplastied iliac arteries. Conclusions-Eplerenone attenuates constrictive remodeling after coronary ar tery angioplasty by mechanisms involving reduction in collagen accumulation , which thus appears to be an important contributor to constrictive remodel ing of angioplastied coronary arteries.