title: Impaired Nitric Oxide Mediated Vasodilation In The Peripheral Circulation In The R6/2 Mouse Model Of Huntington's Disease.
abstract: Recent evidence shows that the Huntington's disease (HD) extends beyond the nervous system to other sites, including the cardiovascular system. Further, the cardiovascular pathology pre-dates neurological decline, however the mechanisms involved remain unclear. We investigated in the R6/2 mouse model of HD nitric oxide (NO) dependent and independent endothelial mechanisms. Femoral artery reactivity was determined by wire myography in wild type (WT) and R6/2 mice at 12 and 16 weeks of adulthood. WT mice showed increased endothelial relaxation between 12 and 16 weeks (Rmax: 72 ± 7% vs. 97 ± 13%, P < 0.05). In contrast, R6/2 mice showed enhanced endothelial relaxation already by 12 weeks (Rmax at 12w: 72 ± 7% vs. 94 ± 5%, WT vs. R6/2, P < 0.05) that declined by 16 weeks compared with WT mice (Rmax at 16w: 97 ± 13% vs. 68 ± 7%, WT vs. R6/2, P < 0.05). In WT mice, the increase in femoral relaxation between 12 and 16 weeks was due to enhanced NO dependent mechanisms. By 16 weeks of adult age, the R6/2 mouse developed overt endothelial dysfunction due to an inability to increase NO dependent vasodilation. The data add to the growing literature of non-neural manifestations of HD and implicate NO depletion as a key mechanism underlying the HD pathophysiology in the peripheral vasculature.
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kane
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: A Jennifer
authors.initials: AJ
authors.lastname: Morton
authors.affiliation: Department of Physiology, Development &Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005269:Femur / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009213:Myography; D009569:Nitric Oxide / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide