title: Elevated catalase and heme oxygenase-1 may contribute to improved postischaemic cardiac function in long-term type 1 diabetes.
abstract: 1. Although increased oxidative stress has been shown repeatedly to be implicated in diabetes, the cardiovascular anti-oxidant state and heart response to ischaemia in long-term Type 1 diabetes remain largely unknown. The present study was designed to observe heart tolerance to ischaemia-reperfusion and endogenous anti-oxidants in the cardiovascular system in long-term hyperglycaemic rats. 2. Hearts from Sprague-Dawley rats surviving up to 6 months with streptozocin-induced severe hyperglycaemia (blood glucose > 20 mmol/L) were isolated and subjected to global ischaemia and reperfusion. Cardiac function, electrocardiogram and anti-oxidants in the myocardium and aorta were examined. In addition, the morphology of the myocardial mitochondria and the in vitro function of aortic vessels were assessed. 3. Hearts from diabetic rats demonstrated lower baseline heart function but had higher postischaemic coronary flow and left ventricular developed pressure compared with their respective controls (P < 0.05). In addition, hearts from diabetic animals had fewer arrhythmias (P < 0.01) and lower left ventricular end-diastolic pressure during reperfusion (P < 0.05). Higher catalase and heme oxygenase-1 content was found in the aorta and myocardium from diabetic rats (P < 0.01). In aortas from diabetic animals, acetylcholine-induced vasodilatation was enhanced and was approximately 15% after inhibition of nitric oxide synthase, compared with 0% in controls. The 15% relaxation was abrogated by heme oxygenase blockade. Mitochondria from the myocardium of diabetic rats showed significant increases in both size and number (P < 0.05). 4. Hearts of long-term Type 1 diabetic rats demonstrated improved recovery of postischaemic cardiac function and reduced reperfusion arrhythmia. Hyperglycaemia may enhance cardiovascular anti-oxidant capacity and mitochondrial neogenesis, which renders the heart resistant to ischaemia and oxidative injury.
authors.affiliation: Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Shen
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Zhong
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Ding
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Bing-Shun
authors.initials: BS
authors.lastname: Wang
authors.forename: Hideaki
authors.initials: H
authors.lastname: Higashino
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000502:physiology*; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D002374:Catalase / Q000096:biosynthesis* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D004789:Enzyme Activation / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000502:physiology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*
chemical_list: D000975:Antioxidants; D002374:Catalase; D051547:Heme Oxygenase-1