Investigating the effect of calcitonin gene-related peptide antagonist and exercise trainings in rat aorta: Mitophagy, mitochondrial biogenesis, and apoptosis

Abstract

Calcitonin Gene Related Peptide (CGRP) is expressed in the cardiovascular system and showed vasodilatory effects. This study aimed to investigate the effects of exercise training and a CGRP antagonist (CGRPi) on the expression of genes involved in mitochondrial dynamics in the aorta. Forty-two male rats were divided into six groups (n=7): 1) Control; 2) Endurance Training (ET); 3) High-Intensity Interval Training (HIIT); 4) CGRP antagonist (CGRPi,10 mg/kg) administered via intraperitoneal injections; 5) CGRPi + ET (CGRPi-ET); and 6) CGRPi + HIIT (CGRPi-HIIT). Protein expression was analyzed using Western blotting, while gene expression was quantified via Real-Time PCR. Both ET and HIIT significantly upregulated eNOS protein and the gene expression of Pgc-1α, Bcl-2, Nrf-1, Sirt3, Parkin, and eNOS. The increase in Bcl-2 expression induced by ET was attenuated by CGRPi in the groups with the combination of CGRPi and ET (P = 0.02). Exercise training enhanced mitochondrial biogenesis by affecting the expression of Pgc-1α, Nrf-1 and Sirt3. While CGRP is known to mediate vasodilation, we indicated that CGRPi did not affect eNOS expression, suggesting that CGRP exerts vasodilatory effects through mechanisms other than eNOS in the aorta. Furthermore, CGRPi does not showed negative effects over genes associated with mitophagy and mitochondrial biogenesis.