Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation
Nitric oxide (<sup>•</sup>NO), a diffusible free radical, is an intercellular messenger, playing a crucial role in several key brain physiological processes, including in neurovascular coupling (NVC). In the brain, glutamatergic activation of the neuronal nitric oxide synthase (nNOS) enz...
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MDPI AG
2023-05-01
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| Series: | BioChem |
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| Online Access: | https://www.mdpi.com/2673-6411/3/2/6 |
| _version_ | 1797596018077859840 |
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| author | Carla Nunes João Laranjinha |
| author_facet | Carla Nunes João Laranjinha |
| author_sort | Carla Nunes |
| collection | DOAJ |
| description | Nitric oxide (<sup>•</sup>NO), a diffusible free radical, is an intercellular messenger, playing a crucial role in several key brain physiological processes, including in neurovascular coupling (NVC). In the brain, glutamatergic activation of the neuronal nitric oxide synthase (nNOS) enzyme constitutes its main synthesis pathway. However, when oxygen (O<sub>2</sub>) supply is compromised, such as in stroke, ischemia, and aging, such <sup>•</sup>NO production pathway may be seriously impaired. In this context, evidence suggests that, as already observed in the gastric compartment, the reduction of nitrite by dietary compounds (such as ascorbate and polyphenols) or by specific enzymes may occur in the brain, constituting an important rescuing or complementary mechanism of <sup>•</sup>NO production. Here, using microsensors selective for <sup>•</sup>NO, we show that nitrite enhanced the <sup>•</sup>NO production in a concentration-dependent manner and in the presence of ascorbate evoked by N-methyl-D-aspartate (NMDA) and glutamate stimulation of rat hippocampal slices. Additionally, nitrite potentiated the <sup>•</sup>NO production induced by oxygen-glucose deprivation (OGD). Overall, these observations support the notion of a redox interaction of ascorbate with nitrite yielding <sup>•</sup>NO upon neuronal glutamatergic activation and given the critical role of NO as the direct mediator of neurovascular coupling may represents a key physiological mechanism by which <sup>•</sup>NO production for cerebral blood flow (CBF) responses to neuronal activation is sustained under hypoxic/acidic conditions in the brain. |
| first_indexed | 2024-03-11T02:45:35Z |
| format | Article |
| id | doaj.art-44f60173952b4f5ba6f6f2cf6e37fb73 |
| institution | Directory Open Access Journal |
| issn | 2673-6411 |
| language | English |
| last_indexed | 2024-03-11T02:45:35Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | BioChem |
| spelling | doaj.art-44f60173952b4f5ba6f6f2cf6e37fb732023-11-18T09:20:32ZengMDPI AGBioChem2673-64112023-05-0132789010.3390/biochem3020006Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor StimulationCarla Nunes0João Laranjinha1Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCenter for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalNitric oxide (<sup>•</sup>NO), a diffusible free radical, is an intercellular messenger, playing a crucial role in several key brain physiological processes, including in neurovascular coupling (NVC). In the brain, glutamatergic activation of the neuronal nitric oxide synthase (nNOS) enzyme constitutes its main synthesis pathway. However, when oxygen (O<sub>2</sub>) supply is compromised, such as in stroke, ischemia, and aging, such <sup>•</sup>NO production pathway may be seriously impaired. In this context, evidence suggests that, as already observed in the gastric compartment, the reduction of nitrite by dietary compounds (such as ascorbate and polyphenols) or by specific enzymes may occur in the brain, constituting an important rescuing or complementary mechanism of <sup>•</sup>NO production. Here, using microsensors selective for <sup>•</sup>NO, we show that nitrite enhanced the <sup>•</sup>NO production in a concentration-dependent manner and in the presence of ascorbate evoked by N-methyl-D-aspartate (NMDA) and glutamate stimulation of rat hippocampal slices. Additionally, nitrite potentiated the <sup>•</sup>NO production induced by oxygen-glucose deprivation (OGD). Overall, these observations support the notion of a redox interaction of ascorbate with nitrite yielding <sup>•</sup>NO upon neuronal glutamatergic activation and given the critical role of NO as the direct mediator of neurovascular coupling may represents a key physiological mechanism by which <sup>•</sup>NO production for cerebral blood flow (CBF) responses to neuronal activation is sustained under hypoxic/acidic conditions in the brain.https://www.mdpi.com/2673-6411/3/2/6nitric oxidenitriteascorbatehippocampal slices |
| spellingShingle | Carla Nunes João Laranjinha Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation BioChem nitric oxide nitrite ascorbate hippocampal slices |
| title | Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation |
| title_full | Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation |
| title_fullStr | Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation |
| title_full_unstemmed | Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation |
| title_short | Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation |
| title_sort | nitric oxide production from nitrite plus ascorbate during ischemia upon hippocampal glutamate nmda receptor stimulation |
| topic | nitric oxide nitrite ascorbate hippocampal slices |
| url | https://www.mdpi.com/2673-6411/3/2/6 |
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