Complex vasoactivity of liraglutide. Contribution of three gasotransmitters

Eszter Sélley; Gergő A. Molnár; Szilárd Kun; István András Szijártó; Boglárka Laczy; Tibor Kovács; Ferenc Fülöp; István Wittmann

doi:10.1016/j.artres.2015.04.001

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Volume 11, Issue C, September 2015, Pages 1 - 9

Complex vasoactivity of liraglutide. Contribution of three gasotransmitters

Authors

Eszter Sélley^a, Gergő A. Molnár^a, Szilárd Kun^a, István András Szijártó^b, Boglárka Laczy^a, Tibor Kovács^a, Ferenc Fülöp^c, István Wittmann^a^{, *}

^a2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

^bMedical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum and Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany

^cInstitute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary

^*Corresponding author. University of Pécs, Faculty of Medicine, 2nd Department of Medicine and Nephrological Center, 1 Pacsirta St., H-7624 Pécs, Hungary. Tel.: +36 72536050; fax: +36 72536051. E-mail address: istvan.wittmann@aok.pte.hu (I. Wittmann).

Corresponding Author

István Wittmann

Received 28 January 2015, Revised 6 March 2015, Accepted 23 April 2015, Available Online 9 May 2015.

DOI: 10.1016/j.artres.2015.04.001 How to use a DOI?
Keywords: Aortic rings; Central (aortic) vasodilatation; GLP-1; Liraglutide
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⁺/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.
Open Access: This is an open access article distributed under the CC BY-NC license.

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Next Article In Issue>

Journal: Artery Research
Volume-Issue: 11 - C
Pages: 1 - 9
Publication Date: 2015/05/09
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.1016/j.artres.2015.04.001 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

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ris enw bib

TY  - JOUR
AU  - Eszter Sélley
AU  - Gergő A. Molnár
AU  - Szilárd Kun
AU  - István András Szijártó
AU  - Boglárka Laczy
AU  - Tibor Kovács
AU  - Ferenc Fülöp
AU  - István Wittmann
PY  - 2015
DA  - 2015/05/09
TI  - Complex vasoactivity of liraglutide. Contribution of three gasotransmitters
JO  - Artery Research
SP  - 1
EP  - 9
VL  - 11
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2015.04.001
DO  - 10.1016/j.artres.2015.04.001
ID  - Sélley2015
ER  -

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