J S Qi1, K W L Kam, M Chen, S Wu, T M Wong. 1. Department of Physiology, The University of Hong Kong, Faculty of Medicine Building, 4/F Laboratory Block, Hong Kong SAR, China.
Abstract
AIMS/HYPOTHESIS: The aim of this study was to determine the effects of preconditioning on injury and expression of heat shock proteins 70 in diabetic rat hearts. METHODS: Diabetes was induced by an intraperitoneal injection of 65 mg kg(-1) streptozotocin. Daily subcutaneous injection of 4 IU insulin started 2 weeks after streptozotocin treatment for 4 weeks. Rats were preconditioned by intravenous injection of 10 mg kg(-1) U50,488H, a selective kappa-opioid receptor agonist (U50,488H preconditioning). The effects of U50,488H preconditioning had previously been shown to be blocked by a selective kappa-opioid receptor antagonist, nor-binaltorphimine. Twenty-four hours later, rats were subjected to 30 min of regional ischaemia by occlusion of the left coronary artery followed by 4 h of reperfusion. Infarct size was determined at the end of reperfusion. Stress-inducible and constitutive heat shock proteins 70 were analysed at the end of ischaemia and reperfusion by Western blotting. RESULTS: Myocardial infarcts induced by ischaemia and reperfusion were greater in diabetic rats. U50,488H preconditioning significantly reduced the infarct size and increased the expression of stress-inducible heat-shock protein 70 in normal rats. The effects of U50,488H preconditioning were abolished in streptozotocin-induced diabetic rats, but restored by insulin replacement. CONCLUSION/ INTERPRETATION: In addition to a greater susceptibility to ischaemic insults, the delayed cardioprotection of U50,488H preconditioning was lost, which could at least partly be due to impaired synthesis of stress-inducible heat-shock protein 70 in diabetic rats.
AIMS/HYPOTHESIS: The aim of this study was to determine the effects of preconditioning on injury and expression of heat shock proteins 70 in diabeticrat hearts. METHODS:Diabetes was induced by an intraperitoneal injection of 65 mg kg(-1) streptozotocin. Daily subcutaneous injection of 4 IU insulin started 2 weeks after streptozotocin treatment for 4 weeks. Rats were preconditioned by intravenous injection of 10 mg kg(-1) U50,488H, a selective kappa-opioid receptor agonist (U50,488H preconditioning). The effects of U50,488H preconditioning had previously been shown to be blocked by a selective kappa-opioid receptor antagonist, nor-binaltorphimine. Twenty-four hours later, rats were subjected to 30 min of regional ischaemia by occlusion of the left coronary artery followed by 4 h of reperfusion. Infarct size was determined at the end of reperfusion. Stress-inducible and constitutive heat shock proteins 70 were analysed at the end of ischaemia and reperfusion by Western blotting. RESULTS:Myocardial infarcts induced by ischaemia and reperfusion were greater in diabeticrats. U50,488H preconditioning significantly reduced the infarct size and increased the expression of stress-inducible heat-shock protein 70 in normal rats. The effects of U50,488H preconditioning were abolished in streptozotocin-induced diabeticrats, but restored by insulin replacement. CONCLUSION/ INTERPRETATION: In addition to a greater susceptibility to ischaemic insults, the delayed cardioprotection of U50,488H preconditioning was lost, which could at least partly be due to impaired synthesis of stress-inducible heat-shock protein 70 in diabeticrats.
Authors: M Joyeux; P Faure; D Godin-Ribuot; S Halimi; A Patel; D M Yellon; P Demenge; C Ribuot Journal: Cardiovasc Res Date: 1999-09 Impact factor: 10.787
Authors: R Marfella; M D'Amico; C Di Filippo; E Piegari; F Nappo; K Esposito; L Berrino; F Rossi; D Giugliano Journal: Diabetologia Date: 2002-06-26 Impact factor: 10.122