[Effects and the mechanism of carvedilol on gap junctional intercellular communication in rat myocardium].
OBJECTIVE
To examine the effects of carvedilol on myocardial ischemia and reperfusion injury and on gap junctional intercellular communication (GJIC).


METHODS
The left coronary artery was occluded for 30 min and reperfused for 4 h. The activity of creatine phosphokinase (CK), lactate dehydrogenase (LDH) and the infarct size were measured. Isolated buffer-perfused hearts were divided randomly into four groups, sham operation (SO), myocardial ischemia and reperfusion (IR), carvedilol (CV) and heptanol (a gap junctional inhibitor) (HT). The effect of carvedilol on GJIC was measured by a modification of Scrape-loading and dye transfer method, and the state of CX43 phosphorylation was evaluated by Western blot.


RESULTS
Compared with the SO group, Increased CK, LDH and infarct size were found in the IR group after 4 h reperfusion. GJIC in the IR group was not inhibited, but dephosphorylated CX43 was increased after 30 minutes of ischemia. Carvedilol decreased CK, LDH and infarct size compared with the IR rats; after 30 minutes of ischemia, both carvedilol and heptanol significantly reduced the GJIC, associated with a significant augmentation of dephosphorylated CX43.


CONCLUSIONS
These results suggest that carvedilol reduces GJIC during ischemia presumably by dephosphorylating Cx43, which may be one of the mechanisms of lessening myocardial ischemia-reperfusion injury.
Fan
Shu-ying
SY
Department of Cardiology, China-Japan Friendship Hospital of Ministry of Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100029, China.
Ke
Yuan-nan
YN
Zeng
Yu-jie
YJ
Wang
Yong
Y
Cheng
Wen-li
WL
Yang
Jian-ru
JR
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002450:Cell Communication / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002227:Carbazoles; D018031:Connexin 43; D011412:Propanolamines; D000077261:Carvedilol