title: 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.
authors: West China School of Medicine, Sichuan University, Chengdu, China.
authors: Yige
authors: Y
authors: Bao
authors: Xiaodong
authors: X
authors: Sun
authors: Yu
authors: Y
authors: Yerong
authors: Lu
authors: L
authors: Shuyuan
authors: Wu
authors: W
authors: Yang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D064233:Sulfonylurea Receptors; D014867:Water / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; C577509:Abcc8 protein, rat; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014867:Water; D005907:Gliclazide; D007545:Isoproterenol