The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced pulmonary hypertension in mice partly via normalization of reduced ETB receptor expression

Title:

The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced pulmonary hypertension in mice partly via normalization of reduced ETB receptor expression

Creator:

Honda, J., Kimura, T., Aonuma, K., Miyauchi, T., Homma, S., Murakoshi, N., Tajiri, K., Maruyama, H., and Sakai, S.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:187f8661-c1ae-4ba1-be36-698d3cac7e66
uuid:187f8661-c1ae-4ba1-be36-698d3cac7e66
issn:0862-8408

Subject:

fyziologie člověka, human physiology, GLP-1R, Pulmonary hypertension, Liraglutide, ETB receptor, eNOS, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH., J. Honda, T. Kimura, S. Sakai, H. Maruyama, K. Tajiri, N. Murakoshi, S. Homma, T. Miyauchi, K. Aonuma., and Seznam literatury

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:Suppl 1

Harvested from:

CDK

Metadata only:

false