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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2020

01-12-2020 | Liraglutide | Original investigation

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

Authors: Vijayakumar Sukumaran, Hirotsugu Tsuchimochi, Takashi Sonobe, Mark T. Waddingham, Mikiyasu Shirai, James T. Pearson

Published in: Cardiovascular Diabetology | Issue 1/2020

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Abstract

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.
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Metadata
Title
Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet
Authors
Vijayakumar Sukumaran
Hirotsugu Tsuchimochi
Takashi Sonobe
Mark T. Waddingham
Mikiyasu Shirai
James T. Pearson
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Liraglutide
Published in
Cardiovascular Diabetology / Issue 1/2020
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-020-01000-z

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