Blockers of sulfonylureas receptor 1 subunits may lead to cardiac protection against isoprenaline-induced injury in obese rats

Recent studies have found that blockers of sulfonylureas receptor 1(SUR1) might have cardiac ischemic protective effects. We evaluated the effects of a selective SUR1 blocker gliclazide on cardiac function and arrhythmia after isoprenaline-induced myocardial injury in obese rats. Diet-induced obese rats received isoprenaline or saline shots subcutaneously. Gliclazide or saline was given q12h for 48h to rats received isoprenaline. We measured ECG and hemodynamic parameters and collected blood samples for CK-MB, glucose and lipid profile determination, and then harvested hearts for water content, histological and immunohistochemical analysis and infarct size measurements. The obese rats' hearts receiving isoprenaline-induced myocardial injury showed up-regulated SUR-1 expression in the peri-microvascular area. Obese rats receiving gliclazide lavage had less severe arrhythmia (ASI: 4.00±0.61 vs. 2.14±0.39, P<0.05) and myocardial edema (water percentage: 85.16±0.46% vs. 81.56±0.57%, P<0.05). Less infarct size (47.6±12.8% vs. 32.7±9.1%, P<0.05) and improved diastolic function (LVEDP: 6.86±0.85% vs. 2.51±1.09%, P<0.05;-(dp/dt)(max): -1663.6±387.91mmHg/s vs. -2834.8±290.76mmHg/s, P<0.05) were also observed in rats receiving gliclazide lavage. Blocking of the SUR1 thus exerts a protective effect on the isoprenaline-induced myocardial injury in obese rats. That SUR1 blocker leads to ischemic protection suggesting a critical biological role of SUR1 in regulating the function of the cardiovascular system than previously recognized under pathophysiological conditions.