Antiarrhythmic effect linked to melatonin cardiorenal protection involves AT₁ reduction and Hsp70-VDR increase

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Chronic kidney disease (CKD) exacerbates lethal ventricular arrhythmias following acute coronary events.
• CKD is linked to myocardial remodeling, oxidative stress, and arrhythmogenesis, with reduced vitamin D receptor (VDR) and increased angiotensin II receptor type 1 (AT ₁ ).
• Melatonin exhibits potential renal and cardiac protective effects, possibly via heat shock protein 70 (Hsp70).

Purpose of the Study:

• To investigate the mechanisms by which melatonin (Mel) prevents kidney damage and arrhythmogenic cardiac remodeling.
• To determine melatonin's effect on oxidative stress, fibrosis, apoptosis, and receptor expression in a unilateral ureteral obstruction (UUO) model.

Main Methods:

• Rats underwent unilateral ureteral obstruction (UUO) or sham surgery and were treated with melatonin (4 mg/kg/day) or vehicle for 15 days.
• Evaluated kidney and heart tissues for VDR, Hsp70, AT ₁ expression, oxidative stress, fibrosis, apoptosis, and mitochondrial morphology.
• Assessed ventricular fibrillation during reperfusion and measured action potential characteristics.

Main Results:

• UUO rats showed reduced VDR and Hsp70, increased AT ₁ , oxidative stress, fibrosis, apoptosis, and mitochondrial abnormalities in kidneys and hearts.
• Melatonin treatment prevented these pathological changes and reduced ventricular fibrillation during reperfusion.
• Melatonin normalized action potential duration and hyperpolarization in UUO rats.

Conclusions:

• Melatonin effectively prevents renal damage and arrhythmogenic myocardial remodeling in the context of unilateral ureteral obstruction.
• The protective effects are attributed to reduced oxidative stress, fibrosis, and apoptosis, alongside decreased AT ₁ and increased Hsp70-VDR expression.
• Melatonin holds promise for managing cardiorenal complications associated with kidney disease.