Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet.

Autor: Sukumaran V; Department of Basic Medical Sciences, College of Medicine, Member of QU Health, Qatar University, Doha, Qatar. Vijay@qu.edu.qa.; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan. Vijay@qu.edu.qa.; Department of Pharmacology, College of Medicine, Member of QU Health, Qatar University, Doha, Qatar. Vijay@qu.edu.qa., Tsuchimochi H; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan., Sonobe T; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan., Waddingham MT; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan.; Department of Advanced Medical Research in Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan., Shirai M; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan., Pearson JT; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, 564-8565, Japan.; Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, 3800, Australia.
Jazyk: angličtina
Zdroj: Cardiovascular diabetology [Cardiovasc Diabetol] 2020 Feb 24; Vol. 19 (1), pp. 24. Date of Electronic Publication: 2020 Feb 24.
DOI: 10.1186/s12933-020-01000-z
Abstrakt: Background: Obesity, hypertension and prediabetes contribute greatly to coronary artery disease, heart failure and vascular events, and are the leading cause of mortality and morbidity in developed societies. Salt sensitivity exacerbates endothelial dysfunction. Herein, we investigated the effect of chronic glucagon like peptide-1 (GLP-1) receptor activation on the coronary microcirculation and cardiac remodeling in Zucker rats on a high-salt diet (6% NaCl).
Methods: Eight-week old Zucker lean (+/+) and obese (fa/fa) rats were treated with vehicle or liraglutide (LIRA) (0.1 mg/kg/day, s.c.) for 8 weeks. Systolic blood pressure (SBP) was measured using tail-cuff method in conscious rats. Myocardial function was assessed by echocardiography. Synchrotron contrast microangiography was then used to investigate coronary arterial vessel function (vessels 50-350 µm internal diameter) in vivo in anesthetized rats. Myocardial gene and protein expression levels of vasoactive factors, inflammatory, oxidative stress and remodeling markers were determined by real-time PCR and Western blotting.
Results: We found that in comparison to the vehicle-treated fa/fa rats, rats treated with LIRA showed significant improvement in acetylcholine-mediated vasodilation in the small arteries and arterioles (< 150 µm diameter). Neither soluble guanylyl cyclase or endothelial NO synthase (eNOS) mRNA levels or total eNOS protein expression in the myocardium were significantly altered by LIRA. However, LIRA downregulated Nox-1 mRNA (p = 0.030) and reduced ET-1 protein (p = 0.044) expression. LIRA significantly attenuated the expressions of proinflammatory and profibrotic associated biomarkers (NF-κB, CD68, IL-1β, TGF-β1, osteopontin) and nitrotyrosine in comparison to fa/fa-Veh rats, but did not attenuate perivascular fibrosis appreciably.
Conclusions: In a rat model of metabolic syndrome, chronic LIRA treatment improved the capacity for NO-mediated dilation throughout the coronary macro and microcirculations and partially normalized myocardial remodeling independent of changes in body mass or blood glucose.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje