Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries.
BACKGROUND
Coronary artery angioplasty triggers healing that causes constrictive remodeling. Because collagen accumulation correlates with constrictive 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 coronary and iliac arteries after angioplasty.


RESULTS
Twenty-four pigs were allocated into 4 treatment groups: oral eplerenone (100 mg/d), oral spironolactone (200 mg/d), subcutaneous aldosterone (400 microgram/d), or no treatment. Twenty-eight days after angioplasty 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-treatment group, without affecting neointima size. These effects were accompanied by a 65% reduction in neointimal and medial collagen density (both P<0.05). Spironolactone was less effective, and aldosterone tended to exert opposite effects on coronary artery structure after angioplasty. These effects were not observed in angioplastied iliac arteries.


CONCLUSIONS
Eplerenone attenuates constrictive remodeling after coronary artery angioplasty by mechanisms involving reduction in collagen accumulation, which thus appears to be an important contributor to constrictive remodeling of angioplastied coronary arteries.
Ward
M R
MR
Baker Medical Research Institute and Alfred Hospital, Melbourne, Victoria, Australia.
Kanellakis
P
P
Ramsey
D
D
Funder
J
J
Bobik
A
A
D000450:Aldosterone / Q000494:pharmacology; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D003251:Constriction, Pathologic / Q000517:prevention & control; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D004549:Elastin / Q000187:drug effects / Q000378:metabolism; D000077545:Eplerenone; D007083:Iliac Artery / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D003094:Collagen; D004549:Elastin