Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 226, Issue 1-2, Pages 83-88Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1012789819926
Keywords
adult rat; cardiac hypertrophy; calcineurin; cyclosporin A; gene expression
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Funding
- NHLBI NIH HHS [R01-HL-62230] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL062230] Funding Source: NIH RePORTER
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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 MHC 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 Ang II treated rats, suggesting that the calcium-calmodulin-dependent calcineurin pathway is associated with angiotensin II induced hypertrophy in vivo.
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