Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production

Cardiovascular Diabetology

Original Investigation

Boglárka Laczy¹  István Wittmann¹  Tibor Kovács¹  Eszter Sélley¹  Gergő A Molnár¹  Szilárd Kun¹  Ferenc Fülöp²  István András Szijártó³ 

[1] 2nd Department of Medicine and Nephrological Center, University of Pécs, Hungary, 1. Pacsirta St, H-7624, Pécs, Hungary;Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, Hungary;Medical 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;

关键词: Glucagon-like-peptide-1;    Exenatide;    Vasodilation;    Aortic rings;    Central blood pressure;   

DOI  :  10.1186/1475-2840-13-69

 received in 2013-12-17, accepted in 2014-03-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIt has been reported that GLP-1 agonist exenatide (exendin-4) decreases blood pressure. The dose-dependent vasodilator effect of exendin-4 has previously been demonstrated, although the precise mechanism is not thoroughly described. Here we have aimed to provide in vitro evidence for the hypothesis that exenatide may decrease central (aortic) blood pressure involving three gasotransmitters, namely nitric oxide (NO) carbon monoxide (CO), and hydrogen sulphide (H2S).MethodsWe determined the vasoactive effect of exenatide on isolated thoracic aortic rings of adult rats. Two millimetre-long vessel segments were placed in a wire myograph and preincubated with inhibitors of the enzymes producing the three gasotransmitters, with inhibitors of reactive oxygen species formation, prostaglandin synthesis, inhibitors of protein kinases, potassium channels or with an inhibitor of the Na+/Ca2+-exchanger.ResultsExenatide caused dose-dependent relaxation of rat thoracic aorta, which was evoked via the GLP-1 receptor and was mediated mainly by H2S but also by NO and CO. Prostaglandins and superoxide free radical also play a part in the relaxation. Inhibition of soluble guanylyl cyclase significantly diminished vasorelaxation. We found that ATP-sensitive-, voltage-gated- and calcium-activated large-conductance potassium channels are also involved in the vasodilation, but that seemingly the inhibition of the KCNQ-type voltage-gated potassium channels resulted in the most remarkable decrease in the rate of vasorelaxation. Inhibition of the Na+/Ca2+-exchanger abolished most of the vasodilation.ConclusionsExenatide induces vasodilation in rat thoracic aorta with the contribution of all three gasotransmitters. We provide in vitro evidence for the potential ability of exenatide to lower central (aortic) blood pressure, which could have relevant clinical importance.

【 授权许可】

Unknown   
© Sélley et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.