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.

Does Intermittent Fasting Improve Microvascular Endothelial Function in Healthy Middle-aged Subjects?

“…Uremic levels of BUN did not induce nitric oxide deficiency in rats with normal renal function, but did so in cultured human and bovine endothelial cells [53]. Elevated BUN may also reflect a negative effect of dehydration on endothelial function and oxidative stress in our study, since Ramadan fasting dictates that no liquids are ingested from sunrise to sunset [54,55]. This could participate to the reduction in BP we observed.…”

Dysfunction of the endothelium and constriction of the isolated rat's middle cerebral artery in low sodium environment in the presence of vasopressin

“…Thus, dysfunctional endothelium of cerebral blood vessels has been reported to secrete endothelin‐1 and vasoconstrictor arachidonic acid derivatives acting on thromboxane receptors . It has been also demonstrated that AVP and activation of vasopressin V 1a receptors, leads to oxidative stress and upregulation of endothelin‐1 in cerebral arterioles . To the best of our knowledge, dysfunction of the endothelium‐dependent control of cerebral blood vessels in hyponatraemia has not been reported before.…”

“…[15][16][17] It has been shown that prolonged increase of AVP concentration in plasma can lead to upregulation of endothelin-1 in the cerebral circulation as well as to increased thromboxane A 2 (TXA 2 ) release. 18,19 The aim of our present study was to find out if the presence of vasopressin during exposure to low Na + concentration increases the tone of the isolated middle cerebral artery (MCA) of the rat.…”

Quantitative proteomics of synaptosome S‐nitrosylation in Alzheimer’s disease

“…Biologically, various mechanisms may cause the differences of synapto‐SNO protein levels observed in the present study. Changes in protein expression prior to nitrosylation (Hong et al ; Papuc ́ et al ), increased NOS2 activity (Chen et al ; Heneka et al ) or other NO sources such as from food and drugs may account for the altered s‐nitrosylation of the synaptosome (Ahmad ; Nakamura et al ; Al‐Gubory ; Faraco et al ), limiting the interpretation of the obtained results. Another factor that increases the production of NO is oxidative stress, which is implicated in the natural aging process as well as a variety of disease states (Tonnies and Trushina ).…”