Angiotensin-converting enzyme inhibitor suppresses activation of calcineurin in renovascular hypertensive rats

Accumulating evidence suggests an important role of the calcineurin signaling pathway in mediating the development of cardiac hypertrophy. It has also been reported that angiotensin-converting enzyme inhibitors (ACEIs)regressed cardiac hypertrophy in some animal and human models. In this study, we investigated the possible role of calcineurin in the regression of cardiac hypertrophy induced by the ACEI perindopril in rats with renovascular hypertension. The effect of the calcineurin inhibitor cyclosporine A (CsA) was also studied. Starting from 2 months after a two-kidney one-clip (2K1C) procedure, the rats that had developed progressive left ventricular (LV) hypertrophy were daily administered perindopril (1 mg/kg per day) or CsA (20 mg/kg per day) until 3 months. At the end of either treatment, the LV gravimetric, morphometric and histological measurements revealed the regression of LV hypertrophy; and the enzymatic assay, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that both calcineurin activity and the calcineurin protein and mRNA expression levels were significantly decreased compared with untreated 2K1C rats, but that LV systolic performance was unchanged by either treatment. These data suggest that the cardiac hypertrophy regression induced by the ACEI perindopril is likely mediated, at least in part, through inhibition of the calcineurin signaling pathway.