Effect of Hyperbaric Oxygen Treatment on Nitric Oxide and Oxygen Free Radicals in Rat Brain

Elayan, Ikram; Axley, Milton J.; Prasad, Paruchuri V.; Ahlers, Stephen T.; Auker, Charles R.

doi:10.1152/jn.2000.83.4.2022

Cited by 133 publications

(82 citation statements)

References 34 publications

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“…In our calculations, the estimated K m value for O 2 was 240-245 μM when the concentration of the other substrate, L-arginine, was varied from 10 to 200 μM. This result is in agreement with the high experimental K m value for NOS1 that has been reported for O 2 (260 μM) [26], although an even higher value (350 μM) was also reported [27].…”

Section: Sensitivity Of No Production To O 2 Tensionsupporting

confidence: 90%

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Chen

Popel

2007

Free Radical Biology and Medicine

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Nitric oxide (NO) derived from nitric oxide synthase (NOS) is an important paracrine effector that maintains vascular tone. The release of NO mediated by NOS isozymes under various O 2 conditions critically determines the NO bioavailability in tissues. Because of experimental difficulties, there has been no direct information on how enzymatic NO production and distribution change around arterioles under various oxygen conditions. In this study, we used computational models based on the analysis of biochemical pathways of enzymatic NO synthesis and the availability of NOS isozymes to quantify the NO production by neuronal NOS (NOS1) and endothelial NOS (NOS3). We compared the catalytic activities of NOS1 and NOS3 and their sensitivities to the concentration of substrate O 2 . Based on the NO release rates predicted from kinetic models, the geometric distribution of NO sources and mass balance analysis, we predicted the NO concentration profiles around an arteriole under various O 2 conditions. The results indicated that NOS1-catalyzed NO production was significantly more sensitive to ambient O 2 concentration than that catalyzed by NOS3. Also, the high sensitivity of NOS1 catalytic activity to O 2 was associated with significantly reduced NO production and therefore NO concentrations, upon hypoxia. Moreover, the major source determining the distribution of NO was NOS1, which was abundantly expressed in the nerve fibers and mast cells close to arterioles, rather than NOS3, which was expressed in the endothelium. Finally, the perivascular NO concentration predicted by the models under conditions of normoxia was paradoxically at least an order of magnitude lower than a number of experimental measurements, suggesting a higher abundance of NOS1 or NOS3 and/or the existence of other enzymatic or nonenzymatic sources of NO in the microvasculature.

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Section: Sensitivity Of No Production To O 2 Tensionsupporting

confidence: 90%

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Chen

Popel

2007

Free Radical Biology and Medicine

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“…This is true not only for neurovascular studies, but also more broadly for studies involving signaling pathways sensitive to O 2 or to reactive oxygen species. For example, neuronal NOS is sensitive to O 2 concentration (K m O 2 of 350 μM, equivalent to ∼266 mm Hg) (30), and high O 2 may alter NO-mediated synaptic regulation in brain slice preparations (31,32).…”

Section: Discussionmentioning

confidence: 99%

Oxygen modulation of neurovascular coupling in the retina

Mishra

Hamid

Newman

2011

Proc. Natl. Acad. Sci. U.S.A.

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Neurovascular coupling is a process through which neuronal activity leads to local increases in blood flow in the central nervous system. In brain slices, 100% O 2 has been shown to alter neurovascular coupling, suppressing activity-dependent vasodilation. However, in vivo, hyperoxia reportedly has no effect on blood flow. Resolving these conflicting findings is important, given that hyperoxia is often used in the clinic in the treatment of both adults and neonates, and a reduction in neurovascular coupling could deprive active neurons of adequate nutrients. Here we address this issue by examining neurovascular coupling in both ex vivo and in vivo rat retina preparations. In the ex vivo retina, 100% O 2 reduced light-evoked arteriole vasodilations by 3.9-fold and increased vasoconstrictions by 2.6-fold. In vivo, however, hyperoxia had no effect on light-evoked arteriole dilations or blood velocity. Oxygen electrode measurements showed that 100% O 2 raised pO 2 in the ex vivo retina from 34 to 548 mm Hg, whereas hyperoxia has been reported to increase retinal pO 2 in vivo to only ∼53 mm Hg [Yu DY, Cringle SJ, Alder VA, Su EN (1994) Am J Physiol 267:H2498-H2507]. Replicating the hyperoxic in vivo pO 2 of 53 mm Hg in the ex vivo retina did not alter vasomotor responses, indicating that although O 2 can modulate neurovascular coupling when raised sufficiently high, the hyperoxia-induced rise in retinal pO 2 in vivo is not sufficient to produce a modulatory effect. Our findings demonstrate that hyperoxia does not alter neurovascular coupling in vivo, ensuring that active neurons receive an adequate supply of nutrients.functional hyperemia | glial cells | prostaglandins N euronal activity in the CNS induces local increases in blood flow (1, 2), a homeostatic response termed functional hyperemia. Neurovascular coupling, the process mediating this response, is thought to involve signaling from neurons to glial cells to blood vessels. Neuronal activity induces a rise in intracellular Ca 2+ in glial cell endfeet surrounding vessels, leading to the release of vasoactive arachidonic acid metabolites and resulting in vasomotor responses (2-6). Experiments in brain slices and in the ex vivo retina have revealed that glial activation can evoke both vasodilation and vasoconstriction. Evoked vasodilations are mediated by cyclooxygenase (COX) products (3, 5) and epoxyeicosatrienoic acids (EETs) (6-9), whereas vasoconstrictions are mediated by 20-hydroxyeicosatetraenoic acid (20-HETE) (4,6).A recent study demonstrated that neurovascular coupling is modulated by O 2 in brain slices (10). Both neuronal and glial cell stimulation elicited vasodilations in brain slices exposed to 20% O 2 . In contrast, vasoconstrictions were evoked in the presence of 100% O 2 . However, another recent study reported the opposite effect of O 2 in vivo (11). In that study, increasing systemic O 2 using hyperbaric hyperoxygenation had no effect on cortical functional hyperemia. Resolving these conflicting findings is critical, given that hyperoxia (breat...

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“…These findings indicate inactivation of NO by superoxide but are inconsistent with autooxidation of NO as a mechanism behind cerebral vasoconstriction during HBO. However, several studies have demonstrated an increase in rat brain nitrite/ nitrate concentration during HBO exposure to 5.0 ATA (18,35) or 3.0 ATA (13). In addition, it has been proposed that autooxidation is of physiological importance when the concentration of oxygen greatly exceeds (by Ͼ6 orders of magnitude) that of superoxide.…”

Section: Ach Relaxation and Enos Activity During Hbo Exposurementioning

confidence: 99%

Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure

Hink¹,

Thom²,

Simonsen³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure. Am J Physiol Heart Circ Physiol 291: H1988 -H1998, 2006. First published April 28, 2006 doi:10.1152/ajpheart.00145.2006.-Accumulating evidence suggests that hyperbaric oxygen (HBO) stimulates neuronal nitric oxide (NO) synthase (NOS) activity, but the influence on endothelial NOS (eNOS) activity and vascular NO bioavailability remains unclear. We used a bioassay employing rat aortic rings to evaluate vascular NO bioavailability. HBO exposure to 2.8 atm absolute (ATA) in vitro decreased ACh relaxation. This effect remained unchanged, despite treatment with SOD-polyethylene glycol and catalase-polyethylene glycol, suggesting that the reduction in endothelium-derived NO bioavailability was independent of superoxide production. In vitro HBO induced contraction of resting aortic rings with and without endothelium, and these contractions were reduced by the NOS inhibitor N -nitro-L-arginine. In addition, in vitro HBO attenuated the vascular contraction produced by norepinephrine, and this effect was reversed by N -nitro-L-arginine, but not by endothelial denudation. These findings indicate stimulation of extraendothelial NO production during HBO exposure. A radiochemical assay was used to assess NOS activity in rat aortic endothelial cells. Catalytic activity of eNOS in cell homogenates was not decreased by HBO, and in vivo HBO exposure to 2.8 ATA was without effect on eNOS activity and/or vascular NO bioavailability in vitro. We conclude that HBO reduces endothelium-derived NO bioavailability independent of superoxide production, and this effect seems to be unrelated to a decrease in eNOS catalytic activity. In addition, HBO increases the resting tone of rat aortic rings and attenuates the contractile response to norepinephrine by endothelium-independent mechanisms that involve extraendothelial NO production. nitric oxide synthase; acetylcholine relaxation; autooxidation HYPERBARIC OXYGEN (HBO) is used in clinical medicine in the management of different diseases and conditions, because it mediates some useful actions, such as stimulation of angiogenesis and inhibition of leukocyte adhesion. However, the underlying biochemical mechanisms have not been fully elucidated.Nitric oxide (NO) bioavailability in rat and mouse cerebral cortex, measured by NO-specific microelectrodes, is increased early during HBO exposure and paralleled by an increase in regional blood flow (40). Thom et al. (40) reported that cerebral NO production was increased much more in knockout mice lacking genes for endothelial NO synthase (eNOS) than in those lacking genes for neuronal NO synthase (nNOS), suggesting that changes in eNOS activity during HBO exposure are minimal compared with changes in nNOS activity. However, because of the predominance of nNOS in the central nervous system (20), this might not be the case in the systemic circulation. Increased nNOS-but not eNOS-derived NO was also observed at the abluminal side of th...

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Effect of Hyperbaric Oxygen Treatment on Nitric Oxide and Oxygen Free Radicals in Rat Brain

Cited by 133 publications

References 34 publications

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

Oxygen modulation of neurovascular coupling in the retina

Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure

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