Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow: Diabetes impairs flow-mediated remodeling
| العنوان: | Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow: Diabetes impairs flow-mediated remodeling |
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| المؤلفون: | Laurent Loufrani, Emilie Vessieres, Eric J. Belin de Chantemèle, Bertrand Toutain, Anne-Laure Guihot, Maud Maquignau, Daniel Henrion |
| المساهمون: | Biologie Neurovasculaire Intégrée (BNVI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Cardiovascular Research Cardiovascular Research, Oxford University Press (OUP), 2008, pp.000. ⟨10.1093/cvr/cvn338⟩ |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, antioxidant, Physiology, Vasodilator Agents, Caveolin 1, Indomethacin, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, arteries, chemistry.chemical_compound, 0302 clinical medicine, Superoxides, blood flow, Splanchnic Circulation, Endothelial dysfunction, Enzyme Inhibitors, remodeling, chemistry.chemical_classification, 0303 health sciences, Membrane Glycoproteins, diabetes, biology, resistance arteries, Adaptation, Physiological, 3. Good health, Mesenteric Arteries, Nitric oxide synthase, Vasodilation, medicine.anatomical_structure, NG-Nitroarginine Methyl Ester, reactive oxigen species, Circulatory system, NADPH Oxidase 2, Cardiology and Cardiovascular Medicine, Artery, medicine.medical_specialty, endothelium, Endothelium, Nitric Oxide Synthase Type III, microcirculation, Nitric oxide, Cyclic N-Oxides, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, medicine, Animals, Ligation, 030304 developmental biology, Reactive oxygen species, Dose-Response Relationship, Drug, business.industry, NADPH Oxidases, medicine.disease, Phosphoproteins, Acetylcholine, Rats, Rats, Zucker, Disease Models, Animal, Oxidative Stress, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Prostaglandin-Endoperoxide Synthases, Regional Blood Flow, biology.protein, Spin Labels, Vascular Resistance, Endothelium, Vascular, business, Oxidative stress |
| الوصف: | International audience; Endothelial dysfunction in resistance arteries leads to end organ damages in type 2 diabetes. The capacity of the microcirculation to adapt or remodel in response to changes in blood flow or shear stress is essential for an optimal organ perfusion. Chronic increases in blood flow enhance arterial diameter and endothelium-dependent dilation.Since type 2 diabetes impairs endothelial sensitivity to flow (shear stress) and increases oxidative stress, we hypothesized that Zucker diabetic fatty rats (ZDF) would present an impaired flow-induced remodeling in resistance artery. Aim: The goal of the study was to compare the structural and functional adaptations of mesenteric arteries from lean (LZ) and ZDF rats, to chronic changes in blood flow. Methods: Two mesenteric resistance arteries were ligated in order to increase blood flow in a third artery. This artery was thus submitted, in vivo, to high flow (HF) and compared to normal flow (NF) arteries located at distance. After 3 weeks arteries were studied in vitro (n= 10 rats per group).Results: Arterial diameter (468 vs 394±8µm) and endothelial (acetylcholine)-dependent dilation (91±8 vs 75±6% dilation) were higher in HF than in NF arteries in LZ rats. In ZDF rats, arterial diameter (396±9 vs 440±17µm) and acetylcholine-mediated dilation (42±8 vs 75±7% dilation) were lower in HF than in NF arteries. Nevertheless, endothelial NO-synthase and NADP(H)-oxidase subunits (gp91, p67) expression level and superoxide production were higher in HF than in NF arteries in both LZ and ZDF rats HF suggesting an efficient flow-sensing process in both ZDF and LZ rats. But, in ZDF rats basal oxidative stress was higher compared to LZ rats: a) dihydroethydium staining was higher in both NF and HF arteries in ZDF than in LZ rats and b) acetylcholine-mediated dilation was improved by an acute antioxidant (tempol) in NF and HF arteries from ZDF rats (no effect in LZ rats NF arteries). As a consequence, oxidative stress, slightly increased in LZ rats HF arteries was strongly increased in ZDF rats HF vessels. This led to an excessive superoxide production impairing NO-dependent dilation and HF-remodeling. Finally, a chronic treatment with tempol restored HF arteries diameter (426±13 in NF vs 471±16µm in HF arteries) and endothelium-dependent dilation in ZDF rats. Conclusion: In type 2 diabetic rats increasing blood flow chronically failed to induce outward remodeling and to improve endothelium-dependent dilation; mainly because of superoxide overproduction. |
| تدمد: | 1755-3245 0008-6363 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e486a01688d90dbaf9afdc13a4824d93Test https://pubmed.ncbi.nlm.nih.gov/19050009Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e486a01688d90dbaf9afdc13a4824d93 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17553245 00086363 |
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