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Abstract

Introduction. Recently, calcineurin has been shown to induce cardiac hypertrophy. Mitogen-activated protein kinases (MAPK), including the extracellular-signal regulated kinases (ERK), the c-Jun NH2-terminal kinases (JNK) and the p38 MAPK (p38), have also been shown to be important in the transduction of trophic signals. The objective of this study was to investigate possible cross-talk between calcineurin and MAPK pathways in controlling renovascular hypertension-induced cardiac hypertrophy.

Methods. Renovascular hypertension was induced by the two kidney-one clip method. The left ventricular weight (LVW) and the ratio of LVW to tibial length were measured to assay the degree of cardiac hypertrophy. Calcineurin activity and MAPK mRNA expression were measured.

Results. In the left ventricle of rats with renovascular hypertension, calcineurin activity and JNK mRNA expression were increased while cardiac hypertrophy developed. Treatment with the calcineurin blocker ciclosporin A induced calcineurin inhibition and regression of cardiac hypertrophy with an improvement of cardiac diastolic function. The treatment also resulted in down-regulation of JNK mRNA expression, but the mRNA expressions of ERK and p38 were unchanged.

Conclusions. There is cross-talk between the calcineurin and JNK pathway in controlling renovascular hypertension-induced cardiac hypertrophy. Inhibition of the calcineurin and JNK pathways may be the basis of reversal of cardiac hypertrophy by calcineurin blockers.

Keywords

calcineurin cardiac hypertrophy mitogen-activated protein kinase rats renovascular hypertension

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Blockade of calcineurin reverses cardiac hypertrophy and induces the down-regulation of JNK mRNA expression in renovascular hypertensive rats

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