The effects of various beta-blockers on myocardial gap junction structure in rat with myocardial ischemia-reperfusion injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of carvedilol, metoprolol and propranolol on myocardial gap junction (GJ) structure in rat with myocardial ischemia and reperfusion injury.</p><p><b>METHODS</b>Rats were divided randomly into five groups: sham operation group (SO), myocardial ischemia and reperfusion group (IR), IR + carvedilol group (CV), IR + metoprolol group (MT), and IR + propranolol group (PP). The left anterior descending branch was ligated for 30 minutes and reperfused for 4 hours (IR). After 4 h reperfusion, the distribution and composition of gap junctional connexin 43 (CX43) were observed by immunofluorescence and laser scanning confocal microscopy (LSCM), and the quantification of CX43 was measured by LSCM.</p><p><b>RESULT</b>Compared with SO group, IR resulted in abnormal distribution and composition of CX43-GJ and the impairment of CX43-GJ was significantly attenuated by CV, MT and PP treatments with the best effect observed in CV group (P<0.05 vs. MT and PP).</p><p><b>CONCLUSION</b>These results suggest that beta-blockers, especially, carvedilol, could significantly attenuate IR induced CX43-GJ impairment.</p>

Role of gap junction in ischemic preconditioning / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the role of gap junction in ischemic preconditioning (IPC).</p><p><b>METHODS</b>Sprague-Dawley rats were subjected to a 30 min coronary artery occlusion followed by 4 h of reperfusion (I/R). Rats were divided into seven groups: I/R, IPC/R, IPC/R + 5-hydroxydecanoic acid (mitochondrial ATP sensitive potassium channel antagonist), I/R + diazoxide (mitochondrial ATP sensitive potassium channel agonist), I/R + 5-hydroxydecanoic acid + diazoxide, I/R + 18beta-glycyrrhetinic acid (gap junction blocker) and I/R + 18beta-glycyrrhetinic acid + 5-hydroxydecanoic acid. Hemodynamics and myocardial infarct size were measured and connexin43 phosphorylation and subcellular distribution were determined by quantitative immunoblotting and confocal immunofluorescence.</p><p><b>RESULTS</b>Infarct size was reduced in IPC/R, I/R + diazoxide and I/R + 18beta-glycyrrhetinic acid group (13.34% +/- 7.87%, 11.02% +/- 2.24%, and 15.03% +/- 11.35%, respectively; P < 0.001 vs. I/R group: 45.81% +/- 7.91%). 5-hydroxydecanoic acid abolished the cardioprotective effects of IPC and diazoxide (46.57% +/- 5.36% and 47.36% +/- 3.17%; P > 0.05 vs. I/R) but not the effects of glycyrrhetinic acid (14.60% +/- 7.36%; P < 0.001 vs. I/R). Phosphorylation of connexin43 was significantly increased, dephosphorylation and connexin43 intracellular redistribution significantly decreased (Cx43 size in the cellular membrane 1.00% +/- 0.35% and 0.83% +/- 0.31%, P < 0.001 vs. I/R: 0.19% +/- 0.06%) by IPC and diazoxide and these effects could be abolished by 5-hydroxydecanoic acid.</p><p><b>CONCLUSION</b>Ischemic preconditioning could reduce myocardial infarction size by activating mitochondrial ATP sensitive potassium channel and modulating connexin43 phosphorylation and internalization.</p>