| Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role of increased osmolarity. | |
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MedLine Citation:
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PMID: 17002667 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is considerable controversy regarding the tolerance of diabetic hearts to ischaemia and the underlying mechanisms responsible for the increased heart tolerance to ischamia remain uncertain. In the present study, we observed, in vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different degrees of hyperglycaemia. In addition, the possible role of increased osmolarity in cardioprotection due to hyperglycaemia was evaluated. Hearts from 3 week streptozocin-induced diabetic rats were isolated and perfused in a Langendorff apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac function and the electrocardiogram were recorded. Myocardial content of osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)-1 and anti-oxidant enzymes were determined in diabetic or hyperosmotic solution-perfused hearts using western blot. The hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; 2 x 10(-7) mol/L) or the nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (1 x 10(-5) mol/L) was added to the perfusate to observe the effects of hsp90 inhibition and hsp90-associated endothelial NOS on ischaemic responses of diabetic hearts. Compared with normal control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20 mmol/L) showed markedly improved postischaemic heart function with fewer reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no significant cardioprotection. Elevated expression of hsp90 accompanied the enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17-AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had markedly elevated HO-1 and catalase, with no significant change in superoxide dismutase. Hyperosmotic perfusion with glucose or mannitol also increased myocardial hsp90 and catalase. The present findings reveal that heart resistance to ischaemia is increased in short-term type 1 diabetes with severe hyperglycaemia. Elevated osmolarity caused by significant hyperglycaemia may contribute to the enhanced myocardial activity against oxidative injury during ischaemia and reperfusion. |
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Authors:
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Hong Chen; Wei-Li Shen; Xu-Hui Wang; Hong-Zhuan Chen; Jian-Zhong Gu; Jie Fu; Ya-Feng Ni; Ping-Jin Gao; Ding-Liang Zhu; Hideaki Higashino |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 33 ISSN: 0305-1870 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-27 Completed Date: 2006-12-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 910-6 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. hchen100@citiz.net |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose Diabetes Mellitus, Experimental / pathology Diabetes Mellitus, Type 1 / chemically induced, pathology* HSP90 Heat-Shock Proteins / metabolism Hyperglycemia / pathology Ischemic Preconditioning, Myocardial / methods Male Myocardial Ischemia / blood, pathology* Osmolar Concentration* Oxidative Stress Rats Reperfusion / methods |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/HSP90 Heat-Shock Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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