{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:08:12Z","timestamp":1760148492777,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-029099","2022.05454.PTDC"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029099","2022.05454.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT","award":["POCI-01-0145-FEDER-029099","2022.05454.PTDC"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029099","2022.05454.PTDC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioChem"],"abstract":"<jats:p>Nitric oxide (\u2022NO), 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 (O2) supply is compromised, such as in stroke, ischemia, and aging, such \u2022NO 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 \u2022NO production. Here, using microsensors selective for \u2022NO, we show that nitrite enhanced the \u2022NO 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 \u2022NO production induced by oxygen-glucose deprivation (OGD). Overall, these observations support the notion of a redox interaction of ascorbate with nitrite yielding \u2022NO 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 \u2022NO production for cerebral blood flow (CBF) responses to neuronal activation is sustained under hypoxic\/acidic conditions in the brain.<\/jats:p>","DOI":"10.3390\/biochem3020006","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T02:28:02Z","timestamp":1683167282000},"page":"78-90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation"],"prefix":"10.3390","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-1592","authenticated-orcid":false,"given":"Carla","family":"Nunes","sequence":"first","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Jo\u00e3o","family":"Laranjinha","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.283.5401.496","article-title":"Energy on demand","volume":"283","author":"Magistretti","year":"1999","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1089\/ars.2013.5669","article-title":"Neurovascular regulation in the ischemic brain","volume":"22","author":"Jackman","year":"2015","journal-title":"Antioxid. 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