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John N Stabley Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Rhonda D Prisby Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Bradley J Behnke Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA
Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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Michael D Delp Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA
Department of Applied Physiology and Kinesiology, Department of Kinesiology and Applied Physiology, Department of Kinesiology, Department of Nutrition, University of Florida, Gainesville, Florida 32611, USA

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, Prisby et al . 2012 ). Cardiovascular disease is a leading complication of T2DM ( Grundy et al . 1999 ), including impairment of endothelium-dependent vasodilation of large conduit arteries ( Hogikyan et al . 1998 , Makimattila et al . 1999 , van de

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Rhonda D Prisby Department of Kinesiology, University of Texas at Arlington, Arlington, Texas, USA

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. The attenuated femoral bone blood flow with advanced age corresponded with reduced endothelium-dependent vasodilation of the femoral PNA ( Prisby et al. 2007 ). Blood flow in long bones are regionally dependent; i.e., hematopoietic marrow and the

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Inmaculada C Villar
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Adrian J Hobbs
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Amrita Ahluwalia Department of Pharmacology, Clinical Pharmacology, University College London, Medical Sciences Building, Gower Street, London WC1E 6BT, UK

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contribute to the beneficial effects in the cardiovascular system i.e. estrogen-induced or enhanced activation of the endothelium. It is now accepted that changes in endothelial function are instrumental in the vascular inflammation that is an early and

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E. E. Änggård
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Think of the endothelium not only as an inert blood container but as a vast endocrine gland. It stretches over the entire vascular tree with a surface area of about 400 square metres, of which most are in the capillaries. Its weight in an adult is about 1 ·5 kg and it contains an estimated 1 ·2 trillion endothelial cells (for review see Gimbrone, 1986; Ryan, 1988). In addition to the obvious barrier and transport functions, the endothelium influences its environment by the secretion of a wide range of biologically active mediators regulating immune responses, vascular tone and coagulation. The endothelium of each organ could therefore be considered to be an endocrine gland in its own right responding to external stimuli by the production of paracrine hormones and growth factors which act on neighbouring smooth muscle cells, monocytes, macrophages, fibroblasts and organ specific cells.

The endothelial cells are remarkably versatile.

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B Torondel
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JM Vila
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G Segarra
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P Lluch
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P Medina
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J Martinez-Leon
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J Ortega
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S Lluch
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The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect was not modified by indomethacin and was only partly reduced by L-NMMA, but was abolished in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA was abolished by using either apamin combined with charybdotoxin, ouabain plus barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent contractions which were of greater magnitude in arteries denuded of endothelium or in the presence of L-NMMA.In conclusion, the results indicate that in human thyroid arteries the endothelium significantly modulates responses to acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a dominant role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.

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N Ghinea
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E Milgrom
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Introduction

In most organs, the vascular endothelium forms a barrier through which the passage of macromolecules is slow and relatively inefficient (Williams 1983). Protein hormones are secreted at very low concentration and act rapidly at their target organs. There is thus a need for specific transendothelial transport mechanisms for these hormones.

We will review here what is known about the structures of endothelial cells in relation to protein transport. We will then describe the specific mechanism we have recently observed for human chorionic gonadotropin/luteinizing hormone (hCG/LH) and discuss its potential generalization to the transendothelial transport of other hormones.

The vascular endothelium constitutes a major barrier for the blood–tissue exchange of macromolecules

The exchange of metabolites and secretory products between the blood and tissues takes place at the level of the microvasculature (i.e. in capillaries and venules). The vascular endothelium is the main barrier although the basal lamina, pericytes

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Verónica Torres-Estay Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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Daniela V Carreño Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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Ignacio F San Francisco Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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Paula Sotomayor Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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Alejandro S Godoy Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile
Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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Gary J Smith Departamento de Fisiología, Urología, Center for Integrative Medicine and Innovative Sciences, Department of Urology, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

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increased monocyte binding to the endothelium. The pathway leading to VCAM-1 expression was dependent of the interaction of functional AR with the NF-κB signaling pathway ( Death et al . 2004 , Nheu et al . 2011 ). In addition, testosterone rapidly

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Derek S Boeldt Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Mary A Grummer Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Ronald R Magness Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Ian M Bird Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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expression as determinants of NO output in uterine artery endothelium: relative roles in pregnancy adaptation and reversal by VEGF 165 . American Journal of Physiology. Heart and Circulatory Physiology 300 H1182 – H1193 . ( doi:10.1152/ajpheart.01108

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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 (UNS), 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 (UNS), San Juan 670, B8000ICN, Bahía Blanca, Argentina

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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 (UNS), 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 (UNS), 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 (UNS), 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 (UNS), San Juan 670, B8000ICN, Bahía Blanca, Argentina

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Introduction The endothelium is the main regulator of vascular physiology that contributes to maintaining vascular tone and non-thrombogenic properties of the endothelial surface. Endothelial nitric oxide (NO) is a key factor in vascular homeostasis

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Jiean Xu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qiuhua Yang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xiaoyu Zhang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zhiping Liu State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yapeng Cao State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Lina Wang State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yaqi Zhou State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Xianqiu Zeng State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Qian Ma State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Yiming Xu Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China

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Yong Wang Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China

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Lei Huang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Zhen Han Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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Tao Wang Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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David Stepp Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Zsolt Bagi Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Chaodong Wu Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, USA

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Mei Hong State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China

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Yuqing Huo Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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Introduction Vascular endothelium plays a crucial role in the regulation of metabolic homeostasis, and dysregulated endothelial function induces the development of metabolic disorders ( Graupera & Claret 2018 , Pi et al. 2018 ). Multiple

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