Purpose: To investigate the changes of phosphorylated ataxia-telangiectasia-mutated (ATM)/ATM and Rad3-related (ATR) substrate and Akt proteins (p-ATM/ATR substrate and p-Akt) and their regulations by
phenylephrine (PE) in the peri-infarct myocardium in rats.
Methods: Myocardial infarction (MI) and Sham-operation were established by Litwin’s method. Three days after operation, surviving Sprague-Dawley male rats were divided into four groups: MI, Sham, MI+PE, and Sham+PE
group. Physiological buffered saline (1 ml/kg) or PE (0.65 mg/kg) were injected into the peritoneal cavity every day for 8 weeks, respectively. Twelve weeks after treatment, p-ATM/ATR substrate and p-Akt expression in myocardium around the infarcted regions were detected by Western blot.
Results: Twelve weeks after treatment, p-ATM/ATR substrate and p-Akt expression were detected throughWestern blot in myocardium around the infarcted regions. The intensity (represented as normalized integrated optical density, IOD) for p-ATM/ATR substrate and p-Akt were (0.59 0.07 and 0.68 0.03) in theMI group, (0.63 0.05 and 0.72 0.04) in the Sham group, (0.99 0.07 and 1.03 0.05) in the MI+PE group and (0.65 0.04 and 0.75 0.04) in the Sham+PE group, respectively. Both presented with significantly increased expression in the MI+PE group as compared with the Sham+PE group (p < 0.05); and in theMI+PE group as compared with theMI group (p < 0.05). No difference was observed between theMI and Sham groups, or between the Sham+PE and Sham groups (p > 0.05).
Conclusion: PE can significantly up-regulate p-ATM/ATR substrate and p-Akt expression and thus might activate ATM/ATR substrate/Akt pathway in myocardium around the infarcted regions. The activated ATM/ATR substrate/Akt pathway might be associated with the attenuation of post-infarction cardiac remodeling, fibrosis, ischemic cardiomyopathy and heart failure induced by PE.