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

DIEZ E. R.; ALTAMIRANO B. L.; GARCÍA I. M.; MAZZEI L. J.; PRADO N. J.; FORNÉS M. W.; CUELLO CARRION F. D.; PONCE ZUMINO A. Z.; FERDER L.; MANUCHA W.

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.