Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats

Abstract

Aims Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure. Methods and resultsWhen male Dahl salt-sensitive rats were fed a high salt (HS) diet, all rats developed cardiac hypertrophy after 5 weeks. Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analogue, at 200 ng, IP 3x/week), enalapril (EP, 90 μg/day), and PC EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC EP groups, but not the V and EP only groups, showed significant prevention of progression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC EP therapy. The expression of PKCα, which is regulated by Ca 2and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC EP effectively decreased PKCα activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment. ConclusionPC treatment resulted in both the prevention of progression of pre-existing cardiac hypertrophy and the development of heart failure, compared with improvement in progression to heart failure by EP alone. These beneficial findings in heart were associated with inhibition of PKCα activation and reversal of gene alterations. © 2011 The Author.