title: Water deprivation induces neurovascular and cognitive dysfunction through vasopressin-induced oxidative stress.
abstract: Adequate hydration is essential for normal brain function and dehydration induces cognitive deterioration. In addition, dehydration has emerged as a stroke risk factor. However, it is unknown whether alterations in cerebrovascular regulation are responsible for these effects. To address this issue, C57Bl/6 mice were water deprived for 24 or 48 hours and somatosensory cortex blood flow was assessed by laser-Doppler flowmetry in a cranial window. Dehydration increased plasma osmolality and vasopressin levels, and suppressed the increase in blood flow induced by neural activity, by the endothelium-dependent vasodilator acetylcholine and the smooth muscle relaxant adenosine. The cerebrovascular dysfunction was associated with oxidative stress and cognitive deficits, assessed using the Y maze. The vasopressin 1a receptor antagonist SR49059 improved the dehydration-induced oxidative stress and vasomotor dysfunction. Dehydration upregulated endothelin-1 in cerebral blood vessels, an effect blocked by SR49059. Furthermore, the endothelin A receptor antagonist BQ123 ameliorated cerebrovascular function. These findings show for the first time that dehydration alters critical mechanisms regulating the cerebral circulation through vasopressin and oxidative stress. The ensuing cerebrovascular dysregulation may alter cognitive function and increase the brain's susceptibility to cerebral ischemia.
authors: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors: Giuseppe
authors: G
authors: Faraco
authors: 1] Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA [2] Department of Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Teodora Stella
authors: TS
authors: Wijasa
authors: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors: Laibaik
authors: L
authors: Park
authors: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors: Jamie
authors: J
authors: Moore
authors: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors: Joseph
authors: J
authors: Anrather
authors: Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors: Costantino
authors: C
authors: Iadecola
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003681:Dehydration / Q000097:blood / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D019332:Endothelin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009994:Osmolar Concentration; D018384:Oxidative Stress; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*; D014868:Water Deprivation / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D019332:Endothelin-1; D014667:Vasopressins