Abstract 1486: Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates Progression to Heart Failure in Dahl Salt-Sensitive Rats
Vitamin D deficiency is a common but often unrecognized condition in patients with heart failure. We previously demonstrated that activated vitamin D (AVD) therapy prevents the progression of cardiac hypertrophy in Dahl salt sensitive (DSS) rats on a high salt (HS) diet ( PNAS 2007; 104 :16810). Here we asked whether AVD can cause pre-existing cardiac hypertrophy to regress and/or attenuate the progression of heart failure.
Methods: To generate cardiac hypertrophy, male DSS rats were fed a HS diet (6% NaCl) from 6 to 11 weeks of age. All animals develop compensated cardiac hypertrophy at 11 weeks, and baseline measurements were obtained (HS-C). The remaining animals divided into three groups:
HS diet with vehicle injection x 4 weeks (HS+V)
HS diet with paricalcitol (PC, 200ng IP 3x/wk) injection x 4 weeks (HS+PC)
normal diet (ND). They were evaluated at 15 weeks.
Results: Compared to hypertrophic baseline (HS-C), the HS+PC group showed a significant reduction in heart weight/tibial length (TL) ratio after 4 weeks (−10 %, p<0.05), whereas the HS+V and ND groups did not (both +2%, p=NS). There were similar reductions compared with baseline in septal and posterior wall thicknesses on echocardiograms (HS+PC: −18% and −20%, respectively, vs. 0% and 0% in HS+V, p<0.05). We also found a significant increase in the lung weight/TL ratio indicative of progressing heart failure in the HS+V group compared with baseline (+73%, p<0.05), which was reduced either by PC treatment or by changing to ND (−18% and −53%, p<0.05 for both). The attenuation of heart failure was also indicated by reductions in LV mass (−7% vs. +20%, p<0.05) and reduced fractional shortening (FS) (−15% vs. −35%, p<0.05) in PC compared to HS+V. Switching to ND, however, resulted in the attenuation of FS only (−11%, p<0.05). We also found a reduction of plasma BNP levels in HS+PC and ND compared to HS+V treated animals (−50% and −59%, P<0.05 for both), and, finally, significantly lower cardiomyocyte hypertrophy and intra-cardiac arteriolar diameter in HS+PC vs. HS+V treated animals.
Conclusion: PC treatment resulted in the regression of pre-existing cardiac hypertrophy in DSS animals. Both PC treatment and a change to a normal diet attenuated the progression of clinical and biochemical signs of heart failure.