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المؤلفSukumaran, Vijayakumar
المؤلفTsuchimochi, Hirotsugu
المؤلفSonobe, Takashi
المؤلفWaddingham, Mark T
المؤلفShirai, Mikiyasu
المؤلفPearson, James T
تاريخ الإتاحة2020-04-01T17:51:12Z
تاريخ النشر2020-02-01
اسم المنشورCardiovascular Diabetologyen_US
المعرّفhttp://dx.doi.org/10.1186/s12933-020-01000-z
الاقتباسSukumaran, V., Tsuchimochi, H., Sonobe, T. et al. Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet. Cardiovasc Diabetol 19, 24 (2020). https://doi.org/10.1186/s12933-020-01000-z
معرّف المصادر الموحدhttp://hdl.handle.net/10576/13758
الملخصObesity, 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). 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. 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. 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.
اللغةen
الناشرBMC
الموضوعEndothelial dysfunction
الموضوعInflammation
الموضوعLiraglutide
الموضوعNitric oxide
الموضوعOxidative stress
العنوانLiraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet.
النوعArticle
ESSN1475-2840


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