title: Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.
abstract: Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact of endothelin receptor blockade (bosentan) on exercise-induced blood flow in the brachial artery and on pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60 ± 7 years old) and control subjects (n = 10, 60 ± 5 years old). Subjects reported twice to the laboratory to perform hand-grip exercise in the presence of endothelin receptor blockade or placebo. We examined brachial artery endothelial function (via flow-mediated dilatation) before and after exercise, as well as blood flow during exercise. Endothelin receptor blockade resulted in a larger increase in blood flow during exercise in type 2 diabetes patients (P = 0.046), but not in control subjects (P = 0.309). Exercise increased shear rate across the exercise protocol, unaffected by endothelin receptor blockade. Exercise did not alter brachial artery diameter in either group, but endothelin receptor blockade resulted in a larger brachial artery diameter in type 2 diabetes patients (P = 0.033). Exercise significantly increased brachial artery flow-mediated dilatation in both groups, unaffected by endothelin receptor blockade. Endothelin receptor blockade increased exercise-induced brachial artery blood flow in type 2 diabetes patients, but not in control subjects. Despite this effect of endothelin receptor blockade on blood flow, we found no impact on baseline or post-exercise endothelial function in type 2 diabetes patients or control subjects, possibly related to normalization of the shear stimulus during exercise. The successful increase in blood flow during exercise in type 2 diabetes patients through endothelin receptor blockade may have beneficial effects in repeated exercise training.
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Tim H A
authors.initials: TH
authors.lastname: Schreuder
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jaap H
authors.initials: JH
authors.lastname: van Lotringen
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Maria T E
authors.initials: MT
authors.lastname: Hopman
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Research Institute for Sports and Exercise Sciences, Liverpool John Moores University, Liverpool, UK dick.thijssen@radboudumc.nl.
authors.forename: Dick H J
authors.initials: DH
authors.lastname: Thijssen
mesh_terms: D000368:Aged; D001783:Blood Flow Velocity; D000077300:Bosentan; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015444:Exercise; D018737:Hand Strength; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012039:Regional Blood Flow; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan