کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5556875 | 1560540 | 2017 | 9 صفحه PDF | دانلود رایگان |
AimsThe vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined.Materials and methodsArterial tone measurement was performed in aortic smooth muscle cells.Key findingsMitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca2Â +-activated K+ (BKCa) channel blocker paxilline, inwardly rectifying K+ (Kir) channel blocker Ba2Â +, and ATP-sensitive K+ (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide. However, application of the voltage-dependent K+ (Kv) channel blocker 4-AP, effectively inhibited mitiglinide-induced vasorelaxation. Although pretreatment with the Ca2Â + channel blocker nifedipine did not alter the mitiglinide-induced vasorelaxation, pretreatment with the sarcoplasmic/endoplasmic reticulum Ca2Â +-ATPase (SERCA) pump inhibitor thapsigargin and cyclopiazonic acid reduced the vasorelaxant effect of mitiglinide. In addition, the vasorelaxant effect of mitiglinide was not affected by the inhibitors of adenylyl cyclase, protein kinase A, guanylyl cyclase, or protein kinase G. Elimination of the endothelium and inhibition of endothelium-dependent vasorelaxant mechanisms also did not change the vasorelaxant effect of mitiglinide.SignificanceWe proposed that mitiglinide induces vasorelaxation via activation of Kv channels and SERCA pump. However, the vasorelaxant effects of mitiglinide did not involve other K+ channels, Ca2Â + channels, PKA/PKG signaling pathways, or the endothelium.
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Journal: Life Sciences - Volume 188, 1 November 2017, Pages 1-9