Aldosterone antagonism fails to attenuate age-associated left ventricular fibrosis.
Collagen accumulates disproportionately in cardiac remodeling induced by hypertension and associated with advancing age. Spironolactone (Spiro), an aldosterone antagonist, attenuates the accumulation of collagen induced by hypertension. It was hypothesized that Spiro would attenuate the age-associated increase in percent collagen in the heart. Female Fisher 344 rats at 3 months (Y), 12 months (M), and 21 months (O) of age were treated with Spiro (30 mg/kg/d) or vehicle (Veh) for 2 months, yielding six groups: Y-Veh, Y-Spiro, M-Veh, M-Spiro, O-Veh, and O-Spiro. Hearts were harvested for immunoblotting, RNA blotting, and biochemical analysis. Percent collagen in the left ventricle and septum was greatest in the oldest rats. Spiro did not significantly attenuate the age-associated increase in collagen fraction or the age-associated increases in expression of atrial natriuretic factor and beta-myosin heavy chain messenger RNA. Chronic aldosterone antagonism does not attenuate the age-associated increase in collagen fraction in the female Fisher 344 rat heart.
Hwang
Hyun Seok
HS
Division of Kinesiology, Laboratory of Molecular Kinesiology, University of Michigan, Ann Arbor, MI 48109-2214, USA.
Cirrincione
Georgina
G
Thomas
D Paul
DP
McCormick
Richard J
RJ
Boluyt
Marvin O
MO
D000375:Aging; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006352:Heart Ventricles; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013148:Spironolactone / Q000494:pharmacology*; D014018:Tissue Distribution; D024723:Ventricular Myosins / Q000235:genetics
D024061:Collagen Type III; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D013148:Spironolactone; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D003094:Collagen; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains