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Alessandra Bitto Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy
Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Domenica Altavilla Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Antonio Bonaiuto Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Francesca Polito Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Letteria Minutoli Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Vincenzo Di Stefano Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Daniela Giuliani Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Salvatore Guarini Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Vincenzo Arcoraci Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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Francesco Squadrito Section of Pharmacology, Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy

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integrity of endothelium was assessed by a relaxant response to ACh (100 nM). The tissue was then washed occasionally for 30 min. Endothelium response was evaluated with cumulative concentrations of ACh (10 nM–1 μM) in aortic rings precontracted with

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Javier Blanco-Rivero Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Ana Sagredo Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Gloria Balfagón Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Mercedes Ferrer Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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exposed to 75 mM KCl to check their functional integrity. After a washout period, the presence of vascular endothelium was tested by the ability of 10 μM ACh to relax segments precontracted with 1 μM noradrenaline (NA). The segments were rinsed

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V L Clifton Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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R Crompton Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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M A Read Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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P G Gibson Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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R Smith Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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I M R Wright Mothers and Babies Research Center, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Neonatal Intensive Care Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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mast cells of the human lung ( Gaston et al. 1994 ) and the skin vascular endothelium ( Abd-El-Aleem et al. 2000 ) suggesting that both of these sites are potential sources of NO in human skin. In our study the inhibition of NOS using N ω -nitro- l

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Adrián E Campelo Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina
Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina

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Pablo H Cutini Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina
Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina

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Virginia L Massheimer Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina
Cátedra de Bioquímica Clínica II, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina

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monocytes) and vascular cells ( Villar et al . 2008 ). Vascular endothelium plays a critical role in the maintenance of antiatherogenic and antithrombotic properties of blood vessels. Besides acting as a selective diffusion barrier, endothelium allows the

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Javier Blanco-Rivero Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Ana Sagredo Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Gloria Balfagón Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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Mercedes Ferrer Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain

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readjusted every 15 min during a 90-min equilibration period before drug administration. After this, the vessels were exposed to 75 mM KCl to check their functional integrity. After a washout period, the presence of vascular endothelium was confirmed by the

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Thanh Q Dang Department of Biology, Faculty of Science York University, Toronto, Canada

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Nanyoung Yoon Department of Biology, Faculty of Science York University, Toronto, Canada

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Helen Chasiotis Department of Biology, Faculty of Science York University, Toronto, Canada

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Emily C Dunford School of Kinesiology and Health Science, Faculty of Health and Muscle Health Research Center, York University, Toronto, Canada

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Qilong Feng Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA

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Pingnian He Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA

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Michael C Riddell School of Kinesiology and Health Science, Faculty of Health and Muscle Health Research Center, York University, Toronto, Canada

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Scott P Kelly Department of Biology, Faculty of Science York University, Toronto, Canada

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Gary Sweeney Department of Biology, Faculty of Science York University, Toronto, Canada

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Introduction As the primary barrier to the movement of circulating endocrine factors from the bloodstream to the interstitial space, the endothelium plays a critical role in hormone action ( Kolka & Bergman 2012 , Yoon et al . 2014

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Mahendra Prasad Bhatt Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Yeon-Ju Lee Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Se-Hui Jung Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Yong Ho Kim SKKU Advanced Institute of Nanotechnology and Department of Chemistry, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea

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Jong Yun Hwang Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Eun-Taek Han Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Won Sun Park Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Seok-Ho Hong Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Young-Myeong Kim Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Kwon-Soo Ha Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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-supplemented diabetic (DM+ins, n  = 11) and both insulin- and C-peptide-supplemented diabetic (DM+ins+CP, n  = 14) mice were dissected and cut longitudinally to expose the endothelium for immediate staining. To measure the intracellular levels, aortic segments were

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Gen Chen School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Xiangjuan Chen Department of Obstetrics and Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Chao Niu The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Xiaozhong Huang The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Ning An School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Jia Sun School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Shuai Huang School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Weijian Ye The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Santie Li School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Yingjie Shen School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Jiaojiao Liang School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Weitao Cong School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Litai Jin School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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, immunofluorescence staining for CD31 (an endothelial cell marker) revealed the presence of de-endothelialized region in aortal endothelium of diabetic mice induced by STZ (100 mg/kg body weight, i.p.) compared with its corresponding control littermates. Systemic

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Alpha Dian-Yu Lin Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Anita Mannikarottu Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Barry A Kogan Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Catherine Whitbeck Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Paul Chichester Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Robert E Leggett Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Robert M Levin Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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. The tissue blocks were sectioned at 5 μm and were used for the immunostaining studies. Immunostaining for vascular endothelium using CD31 Tissue sections were stained with the mouse monoclonal antibody anti-CD31

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Kenichi Serizawa Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Kenji Yogo Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Yoshihito Tashiro Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Satoshi Takeda Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Ryohei Kawasaki Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Ken Aizawa Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Koichi Endo Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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diameter changes after transient ischemia. Transient ischemia leads to reactive hyperemia with increase in flow velocity and vascular wall shear stress. Increased shear stress can induce nitric oxide (NO) production from endothelium, leading to vasodilation

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