Abstract 585: Activated Vitamin D Attenuates Left Ventricular Hypertrophy and Dysfunction in DAHL Salt-Sensitive Rats

Abstract

Introduction: Cardiovascular disease is the leading cause of death among end-stage renal disease (ESRD) patients. Paricalcitrol (PC), an activated vitamin D analog, is associated with improved survival in patients with ESRD. The mechanism of improved mortality, however, is unclear. We hypothesized that administration of PC would attenuate the development of cardiac dysfunction in Dahl salt sensitive (DSS) rats following a high salt (HS) diet, and improve cardiac structure and function in ESRD patients. Methods: Male DSS rats were fed a HS diet (6% NaCl) for 6 weeks beginning at 6 wk of age. PC was administered IP at 200 ng 3x/wk. Animals were evaluated for cardiac function, hemodynamics, mRNA expression of ANF, and plasma BNP levels. Also, a cohort of 77 ESRD patients treated with PC and followed for one year was examined for cardiac function by echocardiogram. Results: Rats on HS + PC compared with HS + vehicle developed significant decrease in heart weight/body weight (HW/BW) ratio (29%, p<0.05) and lung weight/body weight (LW/BW) ratio (27 %, p<0.05). Echocardiogram analysis revealed that PC treatment lead to significant improvement of fractional shortening compared with HS + vehicle treated animals (52.9±1.0 % vs. 45.7±1.6 %, p<0.05). Furthermore, LV pressure measurement showed that PC treatment resulted in significant improvement of LV end diastolic pressure (46%, p<0.05). In addition, significant increase in plasma BNP level was attenuated by PC treatment (67% reduction, p<0.05). PC treatment also significantly attenuated HS diet induced ANF mRNA increase. PC, however, did not have significant change in mean arterial pressure suggesting that beneficial effect seen by PC is not due to lowering of hypertension. In humans, twelve month echo changes in ESRD patients demonstrated that an improvement in E/A ratio and ejection fraction was associated with increasing dose of PC (p<0.05). Conclusion: Administration of PC 3x/week attenuated the development of LVH and LV dysfunction in high salt-induced cardiac hypertrophy and cardiac dysfunction in DSS rats. This finding may also be present in ESRD patients, but these findings remain observational and require confirmation.