Phenylephrine Attenuated Sepsis-Induced Cardiac Inflammation and Mitochondrial Injury Through an Effect on the PI3K/Akt Signaling Pathway

• Published in: Journal of cardiovascular pharmacology Vol. 73; no. 3; p. 186
• Main Authors: Li, Hong-Mei, Li, Kai-Ying, Xing, Yun, Tang, Xiang-Xu, Yang, Duo-Meng, Dai, Xiao-Meng, Lu, Da-Xiang, Wang, Hua-Dong
• Format: Journal Article
• Language: English
• Published: United States 01.03.2019
• Subjects: Animals; Disease Models, Animal; Inflammation Mediators - metabolism; Isolated Heart Preparation; Male; Mitochondria, Heart - drug effects; Mitochondria, Heart - enzymology; Mitochondria, Heart - pathology; Mitochondrial Dynamics - drug effects; Mitochondrial Proteins - metabolism; Myocarditis - enzymology; Myocarditis - etiology; Myocarditis - pathology; Myocarditis - prevention & control; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Myocytes, Cardiac - pathology; Peroxidase - metabolism; Phenylephrine - pharmacology; Phosphatidylinositol 3-Kinase - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats, Sprague-Dawley; Sepsis - complications; Sepsis - drug therapy; Signal Transduction; Stroke Volume - drug effects; Ventricular Function, Left
• ISSN: 1533-4023
• DOI: 10.1097/FJC.0000000000000651

To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway. A rat model of sepsis was established by cecal ligation and puncture. PE and/or wortmannin (a PI3K inhibitor) were administered to investigate the role of PI3K/Akt signaling in mediating the effects of PE on inhibiting sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury. Hematoxylin-eosin staining, echocardiography, and Langendorff system were used to examine the myocardial injury and function. The concentrations of TNF-α and IL-6 were analyzed by enzyme-linked immunosorbent assay. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, mitochondria-related fusion/fission proteins, and PI3K/Akt signaling pathway-associated proteins were analyzed by Western blotting. PE improved the cardiac function and survival in septic rats. PE decreased TNF-α, IL-6, ICAM-1, VCAM-1, and myeloperoxidase contents in the myocardium of septic rats. Meanwhile, PE increased the fusion-related proteins and decreased the fission-related proteins in the myocardial mitochondria of septic rats. On the other hand, PE activated the PI3K/Akt signaling pathway in the cecal ligation and puncture-treated rats, and all the protective effects of PE were abolished by wortmannin. PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.