caa a22 4500 475771346 CHVBK 20180406123618.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s001250051502 doi (NATIONALLICENCE)springer-10.1007/s001250051502 The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate [Elektronische Daten] [A. S. De Vriese, J. Van de Voorde, H. J. Blom, P. M. Vanhoutte, M. Verbeke, N. H. Lameire] Aims/hypothesis. Endothelial dysfunction contributes to the development of diabetic vascular complications. A better understanding of the pathophysiology of endothelial dysfunction in diabetes could lead to new approaches to prevent microvascular disease. Methods. Endothelium-dependent and endothelium-independent vasodilator responses were investigated in the renal microcirculation of streptozotocin-induced diabetic rats. We measured renal blood flow changes with an electromagnetic flow probe. In addition, the responses of the different segments of the renal microcirculation were evaluated with videomicroscopy using the hydronephrotic kidney technique. Because endothelial cells release different relaxing factors (nitric oxide, prostacyclin and an unidentified endothelium-derived hyperpolarizing factor), responses to acetylcholine were measured before and after treatment with the nitric oxide synthase inhibitor l-N G-nitroarginine methylester HCI (l-NAME) and the cyclooxygenase inhibitor indomethacin. We evaluated with the effect of 5-methyltetrahydrofolate, the active form of folate, on the responses. Results. The l-NAME- and indomethacin-resistant vasodilation to intra-renal acetylcholine was significantly reduced in the diabetic compared with control rats, suggesting impaired endothelium-derived hyperpolarizing factor-mediated vasodilation. The responses to the nitric oxide donor (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate) and to the K+-channel opener pinacidil were similar in diabetics and controls, indicating intact endothelium-independent vasodilator mechanisms. The contribution of endothelium-derived hyperpolarizing factor to vasodilation induced by acetylcholine was greatest in the smallest arterioles. In diabetic rats, the response to acetylcholine was increasingly impared as vessel size decreased. Defective vasodilation in diabetic kidneys was rapidly normalized by 5-methyltetrahydrofolate. Conclusion-interpretation. Endothelium-derived hyperpolarizing factor-mediated vasodilation is impaired in the renal microcirculation of diabetic rats, in particular in the smallest arteries. Treatment with folate restores the impaired endothelial function in diabetes. [Diabetologia (2000) 43: 1116-1125] Springer-Verlag Berlin Heidelberg, 2000 Keywords Endothelial dysfunction nationallicence renal microcirculation nationallicence diabetes nationallicence folate nationallicence endothelium-derived hyperpolarizing factor nationallicence acetylcholine nationallicence rat nationallicence renal blood flow nationallicence homocysteine nationallicence De Vriese A. S. The Renal Unit, Ghent University, Belgium, BE aut Van de Voorde J. Department of Physiology, Ghent University, Belgium, BE aut Blom H. J. The Laboratory of Paediatrics and Neurology, University Hospital Nijmegen, The Netherlands, NL aut Vanhoutte P. M. The Servier Research Institute, Suresnes, France, FR aut Verbeke M. The Renal Unit, Ghent University, Belgium, BE aut Lameire N. H. The Renal Unit, Ghent University, Belgium, BE aut https://doi.org/10.1007/s001250051502 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051502 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- De Vriese A. S. The Renal Unit, Ghent University, Belgium, BE aut NATIONALLICENCE 700 1- Van de Voorde J. Department of Physiology, Ghent University, Belgium, BE aut NATIONALLICENCE 700 1- Blom H. J. The Laboratory of Paediatrics and Neurology, University Hospital Nijmegen, The Netherlands, NL aut NATIONALLICENCE 700 1- Vanhoutte P. M. The Servier Research Institute, Suresnes, France, FR aut NATIONALLICENCE 700 1- Verbeke M. The Renal Unit, Ghent University, Belgium, BE aut NATIONALLICENCE 700 1- Lameire N. H. The Renal Unit, Ghent University, Belgium, BE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer