Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial vitamin D receptors deficiency in obstructive nephropathy are reversed by paricalcitol

EMILIANO DIEZ; LILIANA ALTAMIRANO; ISABEL MERCEDES GARCÍA; LUCIANA MAZZEI; NATALIA PRADO; MIGUEL FORNÉS; DARÍO CUELLO-CARRIÓN; AMIRA PONCE ZUMINO; LEÓN FERDER; WALTER MANUCHA

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS

SAGE PUBLICATIONS INC

Lugar: Thousand Oaks, California.; Año: 2015 vol. 20 p. 211 - 220

1074-2484

Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors are among the probable links between the two disorders. The vitamin D?receptor activator paricalcitol protects from some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D?receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D?receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and sham-operated rats were treated with either paricalcitol (30ng/kg/day, ip) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in vitamin D receptors and an increase in angiotensin II type-1 receptor expression (mRNA and protein), suffered fibrosis (determined by Masson?s trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction of myocardial vitamin D?receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D?receptor levels and prolonging action potentials.