The vasorelaxant effect of antidiabetic drug nateglinide via activation of voltage-dependent K+ channels in aortic smooth muscleopen access
- Authors
- Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Seo, Mi Seon; An, Jin Ryeol; Jung, Won-Kyo; Ha, Kwon-Soo; Han, Eun-Taek; Hong, Seok-Ho; Bang, Hyoweon; Choi, Il-Whan; Na, Sung Hun; Park, Won Sun
- Issue Date
- Feb-2018
- Publisher
- WILEY
- Keywords
- Aortic smooth muscle; Nateglinide; Vasorelaxation; Voltage-dependent K+ channel
- Citation
- CARDIOVASCULAR THERAPEUTICS, v.36, no.1
- Journal Title
- CARDIOVASCULAR THERAPEUTICS
- Volume
- 36
- Number
- 1
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1211
- DOI
- 10.1111/1755-5922.12299
- ISSN
- 1755-5914
1755-5922
- Abstract
- AimsWe investigated the vasorelaxant effect of nateglinide and its related mechanisms using phenylephrine (Phe)-induced precontracted aortic rings. MethodsArterial tone measurement was performed in aortic smooth muscle. ResultsThe application of nateglinide induced vasorelaxation in a concentration-dependent manner. Pretreatment with the large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, the inwardly rectifying K+ (Kir) channel inhibitor Ba2+, and ATP-sensitive K+ (K-ATP) channel inhibitor glibenclamide did not affect the vasorelaxant effect of nateglinide. However, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (4-AP) effectively reduced the vasorelaxant effect of nateglinide. Pretreatment with the Ca2+ inhibitor nifedipine and the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin did not change the vasorelaxant effect of nateglinide. Additionally, the vasorelaxant effect of nateglinide was not altered in the presence of an adenylyl cyclase, a protein kinase A, a guanylyl cyclase, or a protein kinase G inhibitor. The vasorelaxant effect of nateglinide was not affected by the elimination of the endothelium. In addition, pretreatment with a nitric oxide synthase inhibitor, L-NAME, and a small-conductance Ca2+-activated K+ (SKCa) channel inhibitor, apamin, did not change the vasorelaxant effect of nateglinide. ConclusionNateglinide induced vasorelaxation via the activation of the Kv channel independent of other K+ channels, Ca2+ channels, intracellular Ca2+ ([Ca2+](i)), and the endothelium.
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