Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT 1 reduction and Hsp70-VDR increase

PRADO, NATALIA JORGELINA; CASAROTTO, MARIANA; CALVO, JUAN PABLO; MAZZEI, LUCIANA; PONCE ZUMINO, AMIRA ZULMA; GARCÍA, ISABEL MERCEDES; CUELLO-CARRIÓN, FERNANDO DARÍO; FORNÉS, MIGUEL WALTER; FERDER, LEÓN; DIEZ, EMILIANO RAÚL; MANUCHA, WALTER

JOURNAL OF PINEAL RESEARCH

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018

0742-3098

Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT1). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase of the heat shock protein 70 (Hsp70) -an antioxidant factor-. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and shamoperated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT1 reduction and Hsp70-VDR increase.