L-type calcium channel blocker suppresses calcineurin signal pathway and development of right ventricular hypertrophy.

Abstract

Many studies have shown that L-type calcium channel blockers can prevent and treat right ventricular hypertrophy (RVH). In order to identify the mechanism, we investigated the role of the calcineurin signal pathway in the progression of RVH induced by chronic hypoxia and the effects of an L-type calcium channel blocker on the pathway. Rats were allocated to 1 of 3 groups (n=10 for each): chronic hypoxia group, amlodipine treatment group (30 mg/kg/day, administered via gavage); and control group. Rats in the amlodipine treatment group and the chronic hypoxia group were exposed to normobaric chronic hypoxia (9.5%-10.5% oxygen). We investigated the changes of right ventricle (RV) to left ventricle (LV) and interventricular septum (S) weight ratio [RV/(LV+S)], RV to body weight (BW) ratio (RV/BW), calcineurin A beta (CnAbeta) mRNA levels, cardiac myosin heavy chain beta (beta-MHC) mRNA levels and protein expression of CnAbeta, nuclear factor 3 of activated T cell (NFAT3), and beta-MHC. After 21 days, RV/(LV+S) and RV/BW were significantly higher in the chronic hypoxia group than in the control group and the amlodipine group (p<0.01). The expression of CnAbeta mRNA and protein, NFAT3 protein, beta-MHC mRNA and protein in RV of the chronic hypoxia group was higher than that of the control group and the amlodipine treatment group (p<0.01). The calcineurin signal pathway plays a critical role in the progression of RVH induced by chronic hypoxia. L-type calcium channel blockade suppresses the development of RVH by inhibiting this pathway.