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

ABSTRACT

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 q12 h for 48 h 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 ± 387.91 mmHg/s vs. -2834.8 ± 290.76 mmHg/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.