{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:37:32Z","timestamp":1792532252729,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kitasato University Research Grant for Young Researchers"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The purpose of this study was to investigate whether quercetin, a flavonoid abundantly found in onion leaves and other plant foods, induces the dilation of retinal blood vessels in rats. The time-course changes in retinal arteriolar diameter were measured using a retinal circulation evaluation system based on a high-resolution digital fundus camera developed in our laboratory. The intravenous administration of quercetin (10\u2013100 \u00b5g\/kg\/min) increased the retinal arteriolar diameter in a dose-dependent manner. This vasodilatory effect of quercetin was almost completely suppressed through an intravitreal pretreatment with N\u03c9-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthase inhibitor. In contrast, the systemic intravenous infusion of quercetin did not cause significant changes in the systemic blood pressure and heart rate. These results suggest that NO production plays an important role in the quercetin-induced dilation of retinal arterioles. Quercetin, which is abundantly present in several plant foods and possesses antioxidant properties, may be a useful agent for the prevention of various ocular diseases associated with visual impairment caused by reduced retinal blood flow.<\/jats:p>","DOI":"10.3390\/ijms27031604","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:33:50Z","timestamp":1770384830000},"page":"1604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin Dilates Retinal Arterioles via Nitric Oxide-Dependent Mechanisms in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-9984","authenticated-orcid":false,"given":"Asami","family":"Mori","sequence":"first","affiliation":[{"name":"Laboratory of Medical Pharmacology, Department of Clinical & Pharmaceutical Sciences, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan"},{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Takimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmacology, Department of Clinical & Pharmaceutical Sciences, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1326-6580","authenticated-orcid":false,"given":"Kenji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Pharmacology, Department of Clinical & Pharmaceutical Sciences, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan"},{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-5870","authenticated-orcid":false,"given":"Tsutomu","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/j.2040-4603.2020.tb00135.x","article-title":"Retinal physiology and circulation: Effect of diabetes","volume":"10","author":"Wright","year":"2020","journal-title":"Compr. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.21037\/atm-21-5695","article-title":"The characteristics of fundus microvascular alterations in the course of glaucoma: A narrative review","volume":"10","author":"Fan","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, M., Liu, H., Mercieca, K., Prinz, J., Feng, Y., and Prokosch, V. (2023). The Association between Vascular Abnormalities and Glaucoma-What Comes First?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713211"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1523\/JNEUROSCI.4048-05.2006","article-title":"Glial cells dilate and constrict blood vessels: A mechanism of neurovascular coupling","volume":"26","author":"Metea","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.preteyeres.2012.04.004","article-title":"Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease","volume":"31","author":"Kur","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jphs.2014.12.014","article-title":"Impaired retinal vasodilator response to acetylcholine in a rat model of NMDA-induced retinal degeneration","volume":"127","author":"Mori","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejphar.2011.07.042","article-title":"Vasodilation of retinal arterioles induced by activation of BKCa channels is attenuated in diabetic rats","volume":"669","author":"Mori","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1080\/02713683.2022.2072896","article-title":"N-Methyl-D-aspartic acid receptor-mediated vasodilation is attenuated in the retinas of diabetic rats","volume":"47","author":"Mori","year":"2022","journal-title":"Curr. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9736047","DOI":"10.1155\/2019\/9736047","article-title":"Elevated Intraocular pressure causes abnormal reactivity of mouse retinal arterioles","volume":"2019","author":"Gericke","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109650","DOI":"10.1016\/j.exer.2023.109650","article-title":"A correlation between oxidative stress and diabetic retinopathy: An updated review","volume":"236","author":"Hussain","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1021\/jf000892m","article-title":"Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants","volume":"49","author":"Miean","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.foodres.2019.03.033","article-title":"Activity profiling of Serbian and some other European Merlot wines in inflammation and oxidation processes","volume":"121","author":"Lesjak","year":"2019","journal-title":"Food Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.lfs.2003.06.039","article-title":"Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta","volume":"74","author":"Ajay","year":"2003","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4196\/kjpp.2009.13.5.361","article-title":"Possible involvement of Ca activated K Channels, SK Channel, in the quercetin-induced vasodilatation","volume":"13","author":"Nishida","year":"2009","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000337182","article-title":"Quercetin induces rapid eNOS phosphorylation and vasodilation by an Akt-independent and PKA-dependent mechanism","volume":"89","author":"Li","year":"2012","journal-title":"Pharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.lfs.2013.02.003","article-title":"Role of gap junction involved with endothelium-derived hyperpolarizing factor for the quercetin-induced vasodilatation in rat mesenteric artery","volume":"92","author":"Nishida","year":"2013","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1055\/s-0034-1368320","article-title":"Enhancement of voltage-gated K+ channels and depression of voltage-gated Ca2+ channels are involved in quercetin-induced vasorelaxation in rat coronary artery","volume":"80","author":"Hou","year":"2014","journal-title":"Planta Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110463","DOI":"10.1016\/j.biopha.2020.110463","article-title":"Plant polyphenols Morin and Quercetin rescue nitric oxide production in diabetic mouse aorta through distinct pathways","volume":"129","author":"Taguchi","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1089\/1080768041223666","article-title":"Structural requirements of flavonoids for increment of ocular blood flow in the rabbit and retinal function recovery in rat eyes","volume":"20","author":"Park","year":"2004","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev.ph.48.030186.001515","article-title":"Modulation of vascular smooth muscle contraction by the endothelium","volume":"48","author":"Vanhoutte","year":"1986","journal-title":"Annu. Rev. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.vph.2006.09.002","article-title":"Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats","volume":"46","author":"Nakazawa","year":"2007","journal-title":"Vascul. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R968","DOI":"10.1152\/ajpregu.91005.2008","article-title":"Nitric oxide dilates rat retinal blood vessels by cyclooxygenase-dependent mechanisms","volume":"297","author":"Ogawa","year":"2009","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1248\/bpb.b20-00220","article-title":"4-Aminopyridine, a voltage-gated K+ channel inhibitor, attenuates nitric oxide-mediated vasodilation of retinal arterioles in rats","volume":"43","author":"Mori","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1248\/bpb.b21-00547","article-title":"Involvement of gap junctions in acetylcholine-induced endothelium-derived hyperpolarization-type dilation of retinal arterioles in rats","volume":"44","author":"Mori","year":"2021","journal-title":"Biol. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1089\/jmf.2017.4052","article-title":"Quercetin-Induced AMP-activated protein kinase activation attenuates vasoconstriction through LKB1-AMPK signaling pathway","volume":"21","author":"Kim","year":"2018","journal-title":"J. Med. Food."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136999","DOI":"10.1016\/j.neulet.2022.136999","article-title":"Resveratrol dilates arterioles and protects against N-methyl-d-aspartic acid-induced excitotoxicity in the rat retina","volume":"793","author":"Mori","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chiang, M.C., Tsai, T.Y., and Wang, C.J. (2023). The Potential benefits of quercetin for brain health: A review of anti-inflammatory and neuroprotective mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076328"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.sjbs.2016.11.017","article-title":"Neuroprotective effects of quercetin in diabetic rat retina","volume":"24","author":"Ola","year":"2017","journal-title":"Saudi. J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"118106","DOI":"10.1016\/j.lfs.2020.118106","article-title":"Quercetin improves vascular endothelial function through promotion of autophagy in hypertensive rats","volume":"258","author":"Lin","year":"2020","journal-title":"Life Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1604\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:35:29Z","timestamp":1770384929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031604"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031604","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}