Erythropoietin alleviates post-resuscitation myocardial dysfunction in rats potentially through increasing the expression of angiotensin II receptor type 2 in myocardial tissues

Zhou,Hourong; Huang,Jia; Zhu,Li; Cao,Yu

doi:10.3892/mmr.2018.8473

Erythropoietin alleviates post-resuscitation myocardial dysfunction in rats potentially through increasing the expression of angiotensin II receptor type 2 in myocardial tissues

Authors:
- Hourong Zhou
- Jia Huang
- Li Zhu
- Yu Cao
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Affiliations: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Emergency Department, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Institute of Anesthesia, Guizhou Medical University, Guiyang, Guizhou 550002, P.R. China
Published online on: January 24, 2018 https://doi.org/10.3892/mmr.2018.8473
Pages: 5184-5192
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Activation of renin-angiotensin system (RAS) is one of the pathological mechanisms associated with myocardial ischemia-reperfusion injury following resuscitation. The present study aimed to determine whether erythropoietin (EPO) improves post‑resuscitation myocardial dysfunction and how it affects the renin‑angiotensin system. Sprague‑Dawley rats were randomly divided into sham, vehicle, epinephrine (EP), EPO and EP + EPO groups. Excluding the sham group, all groups underwent cardiopulmonary resuscitation (CPR) 4 min after asphyxia‑induced cardiac arrest (CA). EP and/or EPO was administrated by intravenous injection when CPR began. The results demonstrated that the vehicle group exhibited lower mean arterial pressure, left ventricular systolic pressure, maximal ascending rate of left ventricular pressure during left ventricular isovolumic contraction and maximal descending rate of left ventricular pressure during left ventricular isovolumic relaxation (+LVdP/dt max and ‑LVdP/dt max, respectively), and higher left ventricular end‑diastolic pressure, compared with the sham group following return of spontaneous circulation (ROSC). Few significant differences were observed concerning the myocardial function between the vehicle and EP groups; however, compared with the vehicle group, EPO reversed myocardial function indices following ROSC, excluding‑LVdP/dt max. Serum renin and angiotensin (Ang) II levels were measured by ELISA. The serum levels of renin and Ang II were significantly increased in the vehicle group compared with the sham group, which was also observed for the myocardial expression of renin and Ang II receptor type 1 (AT1R), as determined by reverse transcription‑quantitative polymerase chain reaction and western blotting. EPO alone did not significantly reduce the high serum levels of renin and Ang II post-resuscitation, but changed the protein levels of renin and AT1R expression in myocardial tissues. However, EPO enhanced the myocardial expression of Ang II receptor type 2 (AT2R) following ROSC. In conclusion, the present study confirmed that CA resuscitation activated the renin‑Ang II‑AT1R signaling pathway, which may contribute to myocardial dysfunction in rats. The present study confirmed that EPO treatment is beneficial for protecting cardiac function post‑resuscitation, and the roles of EPO in alleviating post‑resuscitation myocardial dysfunction may potentially be associated with enhanced myocardial expression of AT2R.

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