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Water deprivation induces neurovascular and cognitive dysfunction through vasopressin-induced oxidative stress.

TitleWater deprivation induces neurovascular and cognitive dysfunction through vasopressin-induced oxidative stress.
Publication TypeJournal Article
Year of Publication2014
AuthorsFaraco G, Wijasa TStella, Park L, Moore J, Anrather J, Iadecola C
JournalJ Cereb Blood Flow Metab
Volume34
Issue5
Pagination852-60
Date Published2014 May
ISSN1559-7016
KeywordsAnimals, Antidiuretic Hormone Receptor Antagonists, Brain, Cerebrovascular Circulation, Cognition Disorders, Dehydration, Endothelin-1, Male, Mice, Mice, Inbred C57BL, Osmolar Concentration, Oxidative Stress, Vasopressins, Water Deprivation
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.

DOI10.1038/jcbfm.2014.24
Alternate JournalJ. Cereb. Blood Flow Metab.
PubMed ID24517977
PubMed Central IDPMC4013763
Grant ListHL096571 / HL / NHLBI NIH HHS / United States
R01 NS037853 / NS / NINDS NIH HHS / United States
R01 NS073666 / NS / NINDS NIH HHS / United States
NS73666 / NS / NINDS NIH HHS / United States
P01 HL096571 / HL / NHLBI NIH HHS / United States