{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:10Z","timestamp":1792277890678,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2022,12,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Neurovascular coupling (NVC) is a key process in cerebral blood flow regulation. NVC ensures adequate brain perfusion to changes in local metabolic demands. Neuronal nitric oxide synthase (nNOS) is suspected to be involved in NVC; however, this has not been tested in humans. Our objective was to investigate the effects of nNOS inhibition on NVC in humans.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We performed a 3-visit partially randomized, double-blinded, placebo-controlled, crossover study in 12 healthy subjects. On each visit, subjects received an intravenous infusion of either S-methyl-L-thiocitrulline (a selective nNOS-inhibitor), 0.9% saline (placebo control), or phenylephrine (pressor control). The NVC assessment involved eliciting posterior circulation hyperemia through visual stimulation while measuring posterior and middle cerebral arteries blood velocity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              nNOS inhibition blunted the rapidity of the NVC response versus pressor control, evidenced by a reduced initial rise in mean posterior cerebral artery velocity (\u22123.3% [\u22126.5, \u22120.01],\n              <jats:italic>P<\/jats:italic>\n              =0.049), and a reduced rate of increase (ie, acceleration) in posterior cerebral artery velocity (slope reduced \u22124.3% [\u22128.5, \u22120.1],\n              <jats:italic>P<\/jats:italic>\n              =0.045). The overall magnitude of posterior cerebral artery response relative to placebo control or pressor control was not affected. Changes in BP parameters were well-matched between the S-methyl-L-thiocitrulline and pressor control arms.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Neuronal NOS plays a role in dynamic cerebral blood flow control in healthy adults, particularly the rapidity of the NVC response to visual stimulation. This work opens the way to further investigation of the role of nNOS in conditions of impaired NVC, potentially revealing a therapeutic target.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.122.321631","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T10:00:26Z","timestamp":1667988026000},"page":"952-961","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans"],"prefix":"10.1161","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2218-4763","authenticated-orcid":true,"given":"Kevin","family":"O\u2019Gallagher","sequence":"first","affiliation":[{"name":"School of Cardiovascular and Metabolic Medicine &amp; Sciences, King\u2019s College London British Heart Foundation Centre of Research Excellence, London, UK (K.O., A.R., R.R., P.J.C., A.M.S.)."},{"name":"NIHR Biomedical Research Centre, Clinical Research Facility, Guy\u2019s and St Thomas NHS Foundation Trust, London, UK (K.O., A.R., P.J.C., A.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan E.","family":"Rosentreter","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada (R.E.R, J.E.S., T.L., G.R.G., S.R.R., A.A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-0808","authenticated-orcid":true,"given":"Jan","family":"Elaine Soriano","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada (R.E.R, J.E.S., T.L., G.R.G., S.R.R., A.A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Roomi","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Medicine &amp; Sciences, King\u2019s College London British Heart Foundation Centre of Research Excellence, London, UK (K.O., A.R., R.R., P.J.C., A.M.S.)."},{"name":"NIHR Biomedical Research Centre, Clinical Research Facility, Guy\u2019s and St Thomas NHS Foundation Trust, London, UK (K.O., A.R., P.J.C., A.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saqib","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, COMSATS University, Sahiwal, Pakistan (S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Lam","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada (R.E.R, J.E.S., T.L., G.R.G., S.R.R., A.A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-8581","authenticated-orcid":true,"given":"Roman","family":"Roy","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Medicine &amp; Sciences, King\u2019s College London British Heart Foundation Centre of Research Excellence, London, UK (K.O., A.R., R.R., P.J.C., A.M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant R.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada (R.E.R, J.E.S., T.L., G.R.G., S.R.R., A.A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-3785","authenticated-orcid":true,"given":"Satish R.","family":"Raj","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Pharmacology, Clinical Neurosciences, Cardiac Sciences, Hotchkiss Brain Institute, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Alberta, Canada (R.E.R, J.E.S., T.L., G.R.G., S.R.R., A.A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-038X","authenticated-orcid":true,"given":"Philip J.","family":"Chowienczyk","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Medicine &amp; 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