Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats

Rong-Hua Zheng,1,2 Xiao-Jie Bai,1 Wei-Wei Zhang,1 Jing Wang,1 Feng Bai,1 Cai-Ping Yan,1 Erskine A James,3 Himangshu S Bose,4 Ning-Ping Wang,1,4 Zhi-Qing Zhao1,41Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Medicine, Linfen Vocational and Technical College, Linfen, Shanxi, People’s Republic of China; 3Department of Internal Medicine, Navicent Health, Macon, GA, USA; 4Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USAObjective: Angiotensin II (Ang II) is known to contribute to the pathogenesis of heart failure by eliciting cardiac remodeling and dysfunction. The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study investigates whether GLP-1 receptor agonist liraglutide inhibits abdominal aortic constriction (AAC)-induced cardiac fibrosis and dysfunction through blocking Ang II type 1 receptor (AT1R) signaling.Methods: Sprague-Dawley rats were subjected to sham operation and abdominal aortic banding procedure for 16 weeks. In treated rats, liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or telmisartan (10 mg/kg/day), the AT1R blocker, was administered by gastric gavage.Results: Relative to the animals with AAC, liraglutide reduced protein level of the AT1R and upregulated the AT2R, as evidenced by reduced ratio of AT1R/AT2R (0.59±0.04 vs. 0.91±0.06, p