caa a22 4500 475771044 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s001250050011 doi (NATIONALLICENCE)springer-10.1007/s001250050011 Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels [Elektronische Daten] [S. Vallejo, J. Angulo, C. Peiró, J. Nevado, A. Sánchez-Ferrer, R. Petidier, C. F. Sánchez-Ferrer, L. Rodríguez-Mañas] Aims/hypothesis. It has been recently shown that glycated human haemoglobin induces endothelial dysfunction in rat vessels by generating superoxide anions that interfere with nitric oxide mediated responses. Our study analysed the effect of glycated human haemoglobin on the endothelium-dependent relaxations of human vessels.¶Methods. Omental microvessels were obtained from patients (without diabetes, hypertension or vascular disease) during surgery and mounted in a small vessel myograph to study their vasoactive responses (vessels from 3-7 patients for each set of experiments).¶Results. Cumulative vasodilatory responses to bradykinin (10 nmol/l to 3 μmol/l) were induced in vessels precontracted with 35-50 mmol/l potassium chloride. Addition of 100 μmol/l N G-nitro-l-arginine methyl ester reduced the relaxation evoked by bradykinin, but preincubation with both N G-nitro-l-arginine methyl ester and 10 μmol/l indomethacin was needed to abolish it. Bradykinin-induced responses were inhibited by 1 μmol/l non-glycated oxyhaemoglobin whereas no effect was obtained with 10 nmol/l oxyhaemoglobin. At these low concentrations (10 nmol/l), glycated human oxyhaemoglobin caused an impairment of bradykinin-induced relaxation when the percentage of glycation was 10 % or higher. This effect was prevented by preincubating the vessels with ascorbic acid (10 μmol/l), superoxide dismutase (100 U/ml) and gliclazide (1 and 10 μmol/l), but not with indomethacin (10 μmol/l), catalase (400-600 U/ml), dimethylthiourea (1 mmol/l) or glibenclamide (10 μmol/l). In vessels preincubated with N G-nitro-l-arginine methyl ester (100 μmol/l), glycohaemoglobin did not add any additional effect.¶Conclusion/interpretation. Highly glycated human oxyhaemoglobin, at physiological plasmatic concentrations, impairs nitric oxide-mediated responses by a mechanism involving superoxide anions but not cyclooxygenase derivatives. [Diabetologia (2000) 43: 83-90]. Springer-Verlag Berlin Heidelberg, 2000 Keywords Glycated haemoglobin, endothelial dysfunction, nitric oxide, superoxide anions, antioxidants, human microvessels nationallicence Vallejo S. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut Angulo J. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut Peiró C. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut Nevado J. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut Sánchez-Ferrer A. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut Petidier R. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut Sánchez-Ferrer C. F. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut Rodríguez-Mañas L. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut https://doi.org/10.1007/s001250050011 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050011 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vallejo S. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Angulo J. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Peiró C. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Nevado J. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Sánchez-Ferrer A. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Petidier R. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Sánchez-Ferrer C. F. Department of Pharmacology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain, ES aut NATIONALLICENCE 700 1- Rodríguez-Mañas L. Research Unit and Service of Geriatrics, University Hospital of Getafe, Getafe, Madrid, Spain, ES aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer