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Complex vasoactivity of liraglutide. Contribution of three gasotransmitters

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Item Type:Article
Title:Complex vasoactivity of liraglutide. Contribution of three gasotransmitters
Creators Name:Selley, E. and Molnar, G.A. and Kun, S. and Szijártó, I.A. and Laczy, B. and Kovacs, T. and Fueloep, F. and Wittmann, I.
Abstract:Background: Incretine hormone glucagon-like peptide-1 (GLP-1) causes dose-dependent relaxation of the thoracic aorta of rats and other arteries via nitric oxide (NO), cAMP and ATP-sensitive potassium channels, however, through a mechanism not thoroughly described. Hereby we aimed to determine the mediators involved in the vasoactive effect of liraglutide. Methods: Isolated rat aortic rings and segments of the femoral artery were mounted in a wire myograph to study the vasoactive effect of liraglutide. Vessels were preincubated either with inhibitors of gasotransmitter-, prostaglandin- or reactive oxygen species-formation, or with inhibitors of protein kinases, potassium channels or the Na(+)/Ca(2+)-exchanger. Results: According to our findings, liraglutide activates endothelial cells and vascular smooth muscle cells leading to the production of NO, carbon monoxide, hydrogen sulphide, superoxide anion, and hydrogen peroxide. Increased production of such relaxing factors promotes the activation of protein kinase– A and –G, resulting in the activation of potassium channels (ATP-sensitive-, voltage-gated-, large-conductance-calcium activated), which profoundly contributes to the activation of the Na(+)/Ca(2+)-exchanger, thereby leading to calcium efflux and smooth muscle relaxation and vasorelaxation. Conclusions: We reveal the contribution of all gasotransmitters in the vasorelaxation induced by liraglutide. We provide ex vivo evidence that liraglutide is capable of causing vasodilatation in the central and peripherial vessels, thereby supporting the clinical observation that it lowers blood pressure.
Keywords:Aortic Rings, Central (Aortic) Vasodilatation, GLP-1, Liraglutide, Animals, Rats
Source:Artery Research
Page Range:1-9
Date:September 2015
Additional Information:Copyright © 2015 Association for Research into Arterial Structure and Physiology. Published by Elsevier B.V. All rights reserved. This is an open access article distributed under the CC BY-NC license.
Official Publication:https://doi.org/10.1016/j.artres.2015.04.001
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