Cardiac calcineurin during transition from hypertrophy to heart failure inrats

We studied an alteration of calcineurin expression in the heart and its mod ification by cyclosporin A and an ACE inhibitor, temocapril, using Dahl sal t-sensitive (DS) rats with hypertensive left ventricular hypertrophy (LVH) and congestive heart failure (CHF). Calcineurin protein expression in the L V myocardium was increased in the LVH stage, but then decreased during CBF transition. Chronic cyclosporin A treatment (10 mg/kg/day), which inhibits calcineurin activity, could not block the increases of LV weight and dimens ions and did not improve the LV systolic function during the CHF transition . In contrast, chronic temocapril treatment (20 mg/kg/day) restored the dow nregulation of calcineurin expression, but progression of the hypertrophic process was inhibited. Therefore, cardiac calcineurin is increased in the h ypertensive LVH and may he involved in the development of the adaptive hype rtrophic process. However, calcineurin expression is downregulated during C HF transition and may no longer play a major role in the pathogenesis of my ocardial hypertrophy in the failing hearts. (C) 2000 Academic Press.