Complex vasoactivity of liraglutide. Contribution of three gasotransmitters

• Main Authors: Eszter Sélley, Gergő A. Molnár, Szilárd Kun, István András Szijártó, Boglárka Laczy, Tibor Kovács, Ferenc Fülöp, István Wittmann
• Format: Article
• Language: English
• Published: Atlantis Press 2015-05-01
• Series: Artery Research
• Subjects: Aortic rings; Central (aortic) vasodilatation; GLP-1; Liraglutide
• Online Access: https://www.atlantis-press.com/article/125925198/view

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+/Ca2+-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+/Ca2+-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.