Carvedilol reduces myocardial no-reflow by decreasing endothelin-1 via activation of the ATP-sensitive K+ channel.
It has been verified that carvedilol can attenuate myocardial no-reflow. However, the effects of carvedilol on adenosine triphosphate-sensitive K(+) (K(ATP)) channel and endothelin-1 (ET-1) are unknown. Forty mini-swines were randomized into 5 study groups: 8 control, 8 carvedilol pretreatment, 8 glibenclamide (K(ATP) channel blocker)-treated, 8 carvedilol and glibenclamide-pre-treated and 8 sham-operated. An acute myocardial infarction(AMI) and reperfusion model was created with a three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion. Compared with the control group, carvedilol significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5+/-4.5% to 24.9+/-4.1%, pathological means: from 82.3+/-1.9% to 25.8+/-4.3% of ligation area, respectively; all p < 0.01) and reduced necrosis size from 98.5+/-1.3% to 74.4+/-4.7% of ligation area, p < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of carvedilol. The beneficial effect of carvedilol on myocardial no-reflow could be due to its effect on ET-1 via the activation of the K(ATP) channel.
Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J L
JL
Zhao
Y J
YJ
Yang
W D
WD
Pei
Y H
YH
Sun
M
M
Zhai
Y X
YX
Liu
R L
RL
Gao
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000097:blood* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature
D000959:Antihypertensive Agents; D002227:Carbazoles; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D011412:Propanolamines; D000077261:Carvedilol; D005905:Glyburide