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However, oxidative stress from ischaemia\u2013reperfusion and oxygen\u2013glucose deprivation\u2010reoxygenation (OGD\/R) is known to uncouple NOS, leading to increased production of reactive oxygen species (ROS). This study investigated whether the inhibition of NOS uncoupling in rat brain microvascular endothelial cells (BMECs) and neurons is cytoprotective against OGD\/R\u2010induced injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      All experiments were conducted in both BMECs and neurons under normoxic conditions and following OGD\/R, with or without\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=5213\">NOS inhibition<\/jats:ext-link>\n                      . Cell viability was assessed using Cell Counting Kit\u20108. Electron spin resonance spectrometry measured ROS and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=2509\">NO<\/jats:ext-link>\n                      production, while mitochondrial membrane potential (MMP) was evaluated using\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=4607\">rhodamine 123<\/jats:ext-link>\n                      fluorescence. Oxygen consumption rate (OCR) was measured to assess mitochondrial respiration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>NOS inhibition improved post\u2010OGD\/R survival in BMECs and neurons accompanied by a reduction in NOS\u2010derived ROS. Interestingly, while BMECs showed both ROS\u2010producing uncoupled NOS and NO\u2010producing coupled NOS, neurons showed NO\u2010producing NOS only. Under normoxic conditions, NOS inhibition reduced mitochondrial respiration in BMECs but increased OCR in neurons. OGD\/R led to impaired mitochondrial respiration in both BMECs and neurons, with further reductions observed following NOS inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>NOS inhibition in BMECs and neurons elicit distinct mitochondrial effects under normoxia but promotes identical paradoxical suppression of mitochondrial respiration in response to OGD\/R. NOS uncoupling instigates post\u2010OGD\/R cellular injury in both BMECs and neurons and is a potential therapeutic target in stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70187","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T07:56:11Z","timestamp":1757750171000},"page":"349-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Paradoxical mitochondrial effects of nitric oxide synthase inhibition following oxygen\u2013glucose deprivation\u2013reoxygenation (OGD\/R) in endothelial cells and neurons"],"prefix":"10.1111","volume":"183","author":[{"given":"Venkata N.","family":"Sure","sequence":"first","affiliation":[{"name":"Department of Pharmacology Tulane University School of Medicine  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siva S. V. 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