Angiotensin II induced cardiac hypertrophy in vivo is inhibited by cyclosporin A in adult rats.
Recently, the calcium-calmodulin-dependent calcineurin pathway has been defined as a central pathway for the induction of cardiac hypertrophy. The purpose of this study was to determine if cardiac hypertrophy in animals chronically treated with angiotensin II (AngII), could be prevented by blocking this pathway with cyclosporin A (CsA). Female Wistar rats were treated with AngII by subcutaneous infusion and injected twice a day with CsA (25 mg/kg) for 7 days. In the AngII treated group there was a 30% increase in the heart/body weight ratio (p < 0.05 vs. control). The increase in heart weight was blocked with CsA. Substantial increases in ANF and betaMHC gene expression were detected in the AngII treated animals, which were either attenuated or blocked with CsA treatment. Thus, this study demonstrates that CsA does prevent the development of cardiac hypertrophy in AngII treated rats, suggesting that the calcium-calmodulin-dependent calcineurin pathway is associated with angiotensin II induced hypertrophy in vivo.
Goldspink
P H
PH
Department of Medicine, University of Illinois at Chicago, 60612, USA.
McKinney
R D
RD
Kimball
V A
VA
Geenen
D L
DL
Buttrick
P M
PM
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006984:Hypertrophy; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D012313:RNA; D016572:Cyclosporine; D019703:Calcineurin; D002118:Calcium