Adaptation to hypoxia prevents disturbances in cerebral blood flow during neurodegenerative process

Abstract

The rats with neurodegenerative brain disorder induced by administration of a toxic fragment of beta-amyloid demonstrate weakened endothelium-dependent dilation of cerebral vessels, which attested to impaired production of endothelial NO. At the same time, toxic beta-amyloid fragment induced the formation of NO depots in the walls of cerebral vessels, which indirectly attests to NO overproduction in the brain tissue. Preadaptation to hypoxia prevented endothelial dysfunction and improved the efficiency of NO storage. Our results suggest that adaptation to hypoxia protects the brain from various changes in NO production during neurodegenerative damage.

Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension

“…Specifically, adaptation to hypoxia produces an antihypertensive effect and improves endothelium-dependent relaxation of blood vessels in stroke-prone spontaneously hypertensive rats [13,14]. Mashina et al [17] showed that adaptation to intermittent hypobaric hypoxia prevented endothelial dysfunction of cerebral blood vessels in experimental Alzheimer's disease. This protection apparently stems from stimulation of nitric oxide synthesis and formation of releasable nitric oxide stores in vascular walls, which not only bind excessive nitric oxide, thereby preventing its toxic effects, but also may function as an additional source of free nitric oxide under conditions of nitric oxide shortage [11].…”

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

“…Cerebral NO stores were absent in control rats, but NAC administration revealed NO stores in both hypoxia-adapted and Ab-treated rats. 114 In rats injected with Ab after IHT adaptation, NO stores were increased compared to nonadapted Ab-treated rats. IHT increased NO storage capacity as reflected by the maximum amount of NO, which can potentially be bound to and then released from NO stores.…”

“…114 Endothelium-dependent cerebral dilation was decreased $77% in experimental AD. Intermittent hypobaric hypoxia (4 h/day for 14 days at 4000 m simulated altitude) prevented completely this endothelial dysfunction; thus, IHT normalized ACh-induced vasodilation to that of non-AD controls.…”

“…150 The protective role of NO stores against NO overproduction in experimental AD was investigated in rats. 114 The size of NO stores was evaluated from the ability of Nacetylcysteine (NAC) to release vasoactive products from intracellular NO stores, thereby increasing cerebral blood flow. 114,148 To prevent the contribution of de novo synthesized NO to the cerebral vasodilatory response, NO stores were estimated in the presence of the NO synthase inhibitor, L-NNA.…”

Mitochondrial function in rat cerebral cortex and hippocampus after short- and long-term hypobaric hypoxia

“…Studies in chronic hypoxic conditions compatible with acclimatization are scarce, even though clinically relevant, because adaptation to hypoxia renders protection to nerve cells of brain Manukhina et al, 2008;Mashina et al, 2006). Taking into account the importance of mitochondria in oxygen homeostasis, the aim of the present work was to evaluate mitochondrial function in cerebral cortex and hippocampus in a model of sustained hypobaric hypoxia (1 and 7 months) that simulates high-altitude (5000 m), in order to precise the mechanisms involved in hypoxia acclimatization.…”