Independent roles of CGRP in cardioprotection and hemodynamic regulation in ischemic postconditioning

Calcitonin gene-related peptide (CGRP) may participate in ischemic post-conditioning (IPost) attenuating myocardial ischemia/reperfusion injury. However, the molecular mechanism underlying the effect of CGRP is still elusive. In this study, we evaluated the difference in hemodynamics, infarct size and CGRP in myocardium and serum of rats after acute myocardial ischemia/reperfusion with and without IPost. A specific antagonist of CGRP receptor, CGRP8-37 was employed to testify the role of endogenous CGRP in IPost. The underlying mechanism was investigated by evaluation of the effect of CGRP on the changes in cytosolic reactive oxygen species, mitochondrial membrane potential and myocyte apoptosis induced by hypoxia/reoxygenation in cultured cardiomyocytes of neonatal rats. The results showed that IPost significantly upgraded CGRP in myocardium and serum with reduced infarct size, independent of the reductions in blood pressures observed in this study. The effects were significantly reversed by CGRP8-37, indicating an involvement of intrinsic CGRP. It was further demonstrated that CGRP effectively reversed the hypoxia/reoxygenation-induced reduction of mitochondrial membrane potential and attenuated the increases of cytosolic reactive oxygen species and cardiomyocyte apoptosis. The findings may demonstrate that CGRP mediates the cardioprotective and vasoactive effects of IPost. Homeostasis of cytosolic reactive oxygen species and mitochondrial membrane potential may be underlying the cardioprotective effect of CGRP.