[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.