Vildagliptin, an Anti-diabetic Drug of the DPP-4 Inhibitor, Induces Vasodilation via Kv Channel and SERCA Pump Activation in Aortic Smooth Muscle.
Cardiovasc Toxicol
; 19(3): 244-254, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30519910
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
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Vasodilatadores
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático
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Inibidores da Dipeptidil Peptidase IV
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Vildagliptina
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Toxicol
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Coréia do Sul