Calcitonin gene-related peptide in aerobic exercise induces collateral circulation development in rat ischemia myocardium.

Abstract Purpose Aerobic exercise may offer favorable effects for coronary perfusion in the myocardial ischemia area, although the underlying molecular mechanisms remain unclear. This study was designed to investigate the effect of aerobic exercise on the collateral circulation in the ischemia myocardium and to evaluate calcitonin gene-related peptide (CGRP) changes during this process. Methods and results Wistar rats were randomly divided into 3 groups of 7 rats each: a sham operated group (Sham), a myocardial ischemia-only group (MI) and a MI plus aerobic exercise group (MI + AE). The rat myocardial ischemia model was established by injecting isoprenaline (2 mg/kg, i.p.). The aerobic exercise training consisted of swimming (40 min/d, 5 d/wk) for 4 weeks. At the end-points, after echocardiographic analysis was performed, blood and ischemia myocardium samples were collected and analyzed by ELISA to quantify the CGRP protein. The dorsal root ganglia were isolated and analyzed by reverse transcription polymerase chain reaction (RT-PCR) to examine the CGRP mRNA expression, and ischemia myocardium capillary density was evaluated by immunohistochemistry. Our data showed that the capillary density in the left ventricle and heart function were significantly decreased with decreased CGRP production in the MI rats, which were reversed by aerobic exercise in the MI + AE rats. Conclusion These results indicate that aerobic exercise may alleviate myocardial ischemia through collateral circulation development with increased CGRP production. CGRP may play an important role in developing the collateral circulation.