Intravenous nicorandil preserves endothelial junctions by decreasing endothelin-1 via activation of ATP-sensitive K+ channel.
BACKGROUND
It has been verified that nicorandil can attenuate myocardial no-reflow. However; the effects of nicorandil on endothelial junctions and Endothelin-1 (ET-1) are unknown.


METHODS
40 mini-swines randomized into 5 study groups: 8 in control, 8 nicorandil pretreatment, 8 in glibenclamide (KATP channel blocker)-treated, 8 in nicorandil and glibenclamide-pretreated and 8 in sham-operated. Acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion.


RESULTS
In control group, plasma ET-1 significantly increased, ET-1 or VE-cadherin level in the reflow and no-reflow myocardium was significantly higher or lower than that in normal myocardium. Compared with the control group, nicorandil significantly decreased plasma ET-1 and myocardial tissue ET-1, maintained VE-cadherin level. However, glibenclamide abrogated the protective effect of nicorandil.


CONCLUSIONS
The beneficial effect of nicorandil on endothelial junctions could be due to its effect on ET-1 via the activation of KATp channel.
Zhao
J-L
JL
Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yang
Y-J
YJ
Zhang
Y-H
YH
Pei
W-D
WD
Sun
Y-H
YH
Zhai
M
M
Gao
R-L
RL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000601:surgery; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007275:Injections, Intravenous; D007365:Intercellular Junctions / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism; D008026:Ligation; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020108:Nicorandil / Q000008:administration & dosage / Q000494:pharmacology*; D054318:No-Reflow Phenomenon / Q000201:enzymology / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012107:Research Design; D013552:Swine; D013556:Swine, Miniature; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D019332:Endothelin-1; D005905:Glyburide; D054086:KATP Channels; D020108:Nicorandil; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D000099152:Cadherin 5