PARADOXICALLY ENHANCED HEART TOLERANCE TO ISCHAEMIA IN TYPE 1 DIABETES AND ROLE OF INCREASED OSMOLARITY
| العنوان: | PARADOXICALLY ENHANCED HEART TOLERANCE TO ISCHAEMIA IN TYPE 1 DIABETES AND ROLE OF INCREASED OSMOLARITY |
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| المؤلفون: | Pingjin Gao, Hong Chen, Xu-Hui Wang, Jian-Zhong Gu, Weili Shen, Dingliang Zhu, Ya-Feng Ni, Jie Fu, Hong-Zhuan Chen, Hideaki Higashino |
| المصدر: | Clinical and Experimental Pharmacology and Physiology. 33:910-916 |
| بيانات النشر: | Wiley, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Blood Glucose, Male, medicine.medical_specialty, Physiology, Myocardial Ischemia, Ischemia, In Vitro Techniques, Endothelial NOS, medicine.disease_cause, Diabetes Mellitus, Experimental, Physiology (medical), Diabetes mellitus, Internal medicine, medicine, Animals, HSP90 Heat-Shock Proteins, Pharmacology, Cardioprotection, Osmotic concentration, biology, business.industry, Osmolar Concentration, medicine.disease, Rats, Nitric oxide synthase, Oxidative Stress, Diabetes Mellitus, Type 1, Endocrinology, Hyperglycemia, Ischemic Preconditioning, Myocardial, Reperfusion, biology.protein, Ischemic preconditioning, business, Oxidative stress |
| الوصف: | 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. |
| تدمد: | 1440-1681 0305-1870 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e870c882ff6a389e46cbe6f952ecf6e8Test https://doi.org/10.1111/j.1440-1681.2006.04463.xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....e870c882ff6a389e46cbe6f952ecf6e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401681 03051870 |
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