title: Calcineurin inhibition attenuates mineralocorticoid-induced cardiac hypertrophy.
abstract: BACKGROUND
  It remains unclear how mineralocorticoids induce cardiac hypertrophy and fibrosis. Recently, activation of the calcium-dependent phosphatase, calcineurin, has been shown to induce cardiac hypertrophy. In the present study, we examine the role of calcineurin in mineralocorticoid-induced cardiac hypertrophy and fibrosis.
  
  
  RESULTS
  Uninephrectomized Wistar-Kyoto rats were placed on a 1.0% NaCl diet and treated with aldosterone (0.75 microg x h(-1)) for 6 weeks with or without the calcineurin inhibitors, FK506 (0.5 mg x kg(-1) x d(-1)) or cyclosporine A (10 mg x kg(-1) x d(-1)). The effect of the angiotensin II type 1 receptor antagonist, losartan (10 mg x kg(-1) x d(-1))on aldosterone-induced cardiac hypertrophy was also studied. Treatment with aldosterone increased the heart weight/body weight ratio, cardiomyocyte size, and collagen amount. The expression of mRNA of both type-III collagen and atrial natriuretic peptide in the heart were increased by aldosterone administration. Both calcineurin activity and its mRNA expression were also increased in aldosterone-induced hypertrophic heart. Treatment with losartan, FK506, or cyclosporine partially prevented aldosterone-induced cardiac hypertrophy and fibrosis.
  
  
  CONCLUSIONS
  These results suggest that calcineurin is involved in the development of cardiac hypertrophy and fibrosis induced by mineralocorticoid excess. Inhibition of calcineurin may therefore prevent cardiac hypertrophy and fibrosis in mineralocorticoid hypertension.
authors.affiliation: Second Department of Internal Medicine, Kanazawa University, Kanazawa, Japan. takeday@im2.m.kanazawa-u.ac.jp
authors.forename: Yoshiyu
authors.initials: Y
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoneda
authors.forename: Masashi
authors.initials: M
authors.lastname: Demura
authors.forename: Mikiya
authors.initials: M
authors.lastname: Usukura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000450:Aldosterone; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001835:Body Weight; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D024061:Collagen Type III / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006321:Heart / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008901:Mineralocorticoids; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D065095:Calcineurin Inhibitors; D024061:Collagen Type III; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D008901:Mineralocorticoids; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor; D019703:Calcineurin; D019808:Losartan; D016559:Tacrolimus