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Cardiovascular Toxicology
Erschienen in: Cardiovascular Toxicology 3/2019

05.12.2018

Vildagliptin, an Anti-diabetic Drug of the DPP-4 Inhibitor, Induces Vasodilation via Kv Channel and SERCA Pump Activation in Aortic Smooth Muscle

verfasst von: Mi Seon Seo, Hongliang Li, Jin Ryeol An, In Duk Jung, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park

Erschienen in: Cardiovascular Toxicology | Ausgabe 3/2019

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Abstract

This study investigated vildagliptin-induced vasodilation and its related mechanisms using phenylephrine induced precontracted rabbit aortic rings. Vildagliptin induced vasodilation in a concentration-dependent manner. Pretreatment with the large-conductance Ca2+-activated K+ channel blocker paxilline, ATP-sensitive K+ channel blocker glibenclamide, and inwardly rectifying K+ channel blocker Ba2+ did not affect the vasodilatory effects of vildagliptin. However, application of the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine significantly reduced the vasodilatory effects of vildagliptin. In addition, application of either of two sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitors, thapsigargin or cyclopiazonic acid, effectively inhibited the vasodilatory effects of vildagliptin. These vasodilatory effects were not affected by pretreatment with adenylyl cyclase, protein kinase A (PKA), guanylyl cyclase, or protein kinase G (PKG) inhibitors, or by removal of the endothelium. From these results, we concluded that vildagliptin induced vasodilation via activation of Kv channels and the SERCA pump. However, other K+ channels, PKA/PKG-related signaling cascades associated with vascular dilation, and the endothelium were not involved in vildagliptin-induced vasodilation.
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Metadaten
Titel
Vildagliptin, an Anti-diabetic Drug of the DPP-4 Inhibitor, Induces Vasodilation via Kv Channel and SERCA Pump Activation in Aortic Smooth Muscle
verfasst von
Mi Seon Seo
Hongliang Li
Jin Ryeol An
In Duk Jung
Won-Kyo Jung
Kwon-Soo Ha
Eun-Taek Han
Seok-Ho Hong
Il-Whan Choi
Won Sun Park
Publikationsdatum
05.12.2018
Verlag
Springer US
Erschienen in
Cardiovascular Toxicology / Ausgabe 3/2019
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-018-9496-5

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