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Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT 1 reduction and Hsp70‐ VDR increase
Author(s) -
Prado Natalia Jorgelina,
Casarotto Mariana,
Calvo Juan Pablo,
Mazzei Luciana,
Ponce Zumino Amira Zulma,
García Isabel Mercedes,
CuelloCarrión Fernando Darío,
Fornés Miguel Walter,
Ferder León,
Diez Emiliano Raúl,
Manucha Walter
Publication year - 2018
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12513
Subject(s) - melatonin , medicine , endocrinology , oxidative stress , angiotensin ii , fibrosis , kidney disease , calcitriol receptor , angiotensin ii receptor type 1 , kidney , cardiorenal syndrome , myocardial fibrosis , receptor
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 ( AT 1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in 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 sham‐operated 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 AT 1 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 AT 1 reduction and Hsp70‐ VDR increase.