In:
Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 73, No. 3 ( 2019-03), p. 186-194
Abstract:
To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway. Methods: 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. Results: 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. Conclusions: PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.
Type of Medium:
Online Resource
ISSN:
0160-2446
DOI:
10.1097/FJC.0000000000000651
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
detail.hit.zdb_id:
2049700-3
SSG:
15,3
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