title: Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.
abstract: Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation.
authors.affiliation: Laboratoire de Pharm-Ecologie Cardiovasculaire (EA4278), Faculty of Sciences, Avignon University, Avignon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Battault
authors.affiliation: E.A. 3072, Fédération de Médecine Translationnelle, Faculty of Medicine, University of Strasbourg, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Singh
authors.affiliation: Laboratoire de Pharm-Ecologie Cardiovasculaire (EA4278), Faculty of Sciences, Avignon University, Avignon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gayrard
authors.affiliation: E.A. 3072, Fédération de Médecine Translationnelle, Faculty of Medicine, University of Strasbourg, Strasbourg, France.
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.affiliation: Laboratoire de Pharm-Ecologie Cardiovasculaire (EA4278), Faculty of Sciences, Avignon University, Avignon, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Reboul
authors.affiliation: Laboratoire de Pharm-Ecologie Cardiovasculaire (EA4278), Faculty of Sciences, Avignon University, Avignon, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Meyer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D015308:Anaerobic Threshold; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology / Q000628:therapy; D007537:Isometric Contraction; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine