An orexin-receptor-2-mediated heart-brain axis in cardiac pain
Han Jiao,
Yongjin Wang,
Kang Fu,
Xiaoao Xiao,
Mo-Qiu Jia,
Jia Sun,
Jingxiao Wang,
Guoqing Zhu,
Daying Lyu,
Qiulun Lu,
Yu Peng,
Juan Lv,
Li Su,
Yuanqing Gao
Affiliations
Han Jiao
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China; Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands
Yongjin Wang
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Kang Fu
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Xiaoao Xiao
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Mo-Qiu Jia
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Jia Sun
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Jingxiao Wang
Department of Physiology, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Guoqing Zhu
Department of Physiology, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Daying Lyu
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Qiulun Lu
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Yu Peng
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China
Juan Lv
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
Li Su
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
Yuanqing Gao
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China; Corresponding author
Summary: Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.
