Please use this identifier to cite or link to this item: http://nuir.lib.nu.ac.th/dspace/handle/123456789/6583
Title: Protective effects of selective adenosine-triphosphate sensitive potassium channel modulators on endothelial cells against ischemia-reperfusion injury
ผลการปกป้องของตัวปรับเปลี่ยนช่องไอออนโปตัสเซียมที่ขึ้นกับอะดีโนซีน-ไตรฟอสเฟตชนิดเฉพาะเจาะจงต่อเซลล์เอนโดทีเลียมในการตอบสนองต่อการบาดเจ็บจากภาวะขาดเลือดและการไหลเวียนกลับ               
Authors: Suchada Meeyos
สุชาดา มียศ
Duangduan Siriwittayawan
ดวงเดือน สิริวิทยาวรรณ
Naresuan University
Duangduan Siriwittayawan
ดวงเดือน สิริวิทยาวรรณ
duangduans@nu.ac.th
duangduans@nu.ac.th
Keywords: KATP channel
ATP sensitive potassium channel
Endothelial cell
Ischemic reperfusion injury
Issue Date:  19
Publisher: Naresuan University
Abstract: Background and objectives: Increasing evidence suggested the roles of endothelial cells and ATP-sensitive potassium channels (KATP channels) in cardioprotection during cardiac surgery.  However, there are limited data demonstrating the effects of endothelial KATP activators on endothelial cell viability and NO production in the absence and the presence of hyperkalemic cardioplegia (CPG) against ischemia-reperfusion injury (IRI). The aims of this study were to investigate the early and late effects of IRI with or without selective KATP channel activators on endothelial cell viability and nitric oxide production, in normal conditions and after exposure to hyperkalemic cardioplegia. Method:  Human umbilical vein endothelial cell line (EA.hy926) were cultured in a standard condition for 24 hr and were subsequently subjected to ischemia-reperfusion with or without KATP channel modulators, pinacidil, diazoxide, nicorandil and ZD0947.  Cell viability and NO production were assessed after 10 min and 24-hr of reperfusion. To test the effects of hyperkalemic cardioplegia, the cells were subjected to ischemia and reperfusion of CPG alone or KATP channel modulator -added CPG. To test the effects of nicorandil and ZD0947 following CPG administration, the cells were treated with openers after exposure to CPG.   Cell viability and NO level were investigated after 30 minutes and 24 hours reperfusion. Result: IRI- induced endothelial cell death was decreased significantly in the presence of KATP openers, pinacidil, diazoxide, nicorandil and ZD0947 both at 10 minute and 24 hr reperfusion. After 30 minutes of reperfusion, the NO production was also significantly lower in pinacidil, diazoxide and nicorandil groups when compared to control, IRI and ZD0947 groups. In the late response, it was shown that NO production of nicorandil and ZD0947 treated group was significantly higher than that of the IRI group. Pinacidil or diazoxide- added cardioplegia could improve cell viability against hyperkalemia with IRI, whereas nicorandil and ZD failed. However, adding nicorandil or ZD0947 at the reperfusion period showed the protective effect  against IRI with CPG.  Nicorandil and ZD0947 added-reperfusion solution reduced endothelial cells death in the early phase with relative cell viability of 74.17 ± 1.65 (p = 0.913 vs. I-CPGR) and 74.14 ± 1.62% (p = 0.913 vs. I-CPGR), respectively. However, in late response, cell viability of nicorandil and ZD0947 did not differ from that of I-CPGR group. ZD0947 and nicorandil showed the protective effect on endothelial cell function by increasing NO level in IRI in combination with CPGat the early phase. However, NO levels of all groups returned to the normal level after 24 hr reperfusion.  Conclusion: Ischemia-reperfusion jeopardized endothelial cell viability and function in normokalemia condition and in hyperkalemic CPG. KATP channel openers; pinacidil, diazoxide, nicorandil and ZD0947 ameliorated cell death from IRI. In the presence of cardioplegia, ZD0947 and nicorandil showed the protective effect on endothelial cells function by increasing and maintaining NO production against IRI.
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URI: http://nuir.lib.nu.ac.th/dspace/handle/123456789/6583
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