Abstract | BACKGROUND: 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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Authors | Vijayakumar Sukumaran, Hirotsugu Tsuchimochi, Takashi Sonobe, Mark T Waddingham, Mikiyasu Shirai, James T Pearson |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 19
Issue 1
Pg. 24
(02 24 2020)
ISSN: 1475-2840 [Electronic] England |
PMID | 32093680
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Glp1r protein, rat
- Glucagon-Like Peptide-1 Receptor
- Hypoglycemic Agents
- Incretins
- Sodium Chloride, Dietary
- Nitric Oxide
- Liraglutide
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Topics |
- Animals
- Coronary Artery Disease
(etiology, metabolism, physiopathology, prevention & control)
- Coronary Circulation
(drug effects)
- Disease Models, Animal
- Glucagon-Like Peptide-1 Receptor
(agonists, metabolism)
- Hypertension
(drug therapy, etiology, metabolism, physiopathology)
- Hypoglycemic Agents
(pharmacology)
- Incretins
(pharmacology)
- Insulin Resistance
- Liraglutide
(pharmacology)
- Male
- Microcirculation
(drug effects)
- Nitric Oxide
(metabolism)
- Obesity
(complications, drug therapy, metabolism, physiopathology)
- Oxidative Stress
(drug effects)
- Rats, Zucker
- Sodium Chloride, Dietary
- Ventricular Remodeling
(drug effects)
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