Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.

Cardiovascular Research
Kevin O'GallagherAjay M Shah

Abstract

Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signalling is implicated in cerebrovascular ischaemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesized that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow (CBF), as well as changes in functional brain connectivity. We investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF and brain functional connectivity in healthy human volunteers (n = 19). We performed a randomized, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. SMTC infusion induced an ∼4% decrease in resting global CBF [-2.3 (-0.3, -4.2) mL/100g/min, mean (95% confidence interval, CI), P = 0.02]. In a whole-brain voxel-wise factorial-design comparison of...Continue Reading

References

Apr 1, 1992·The Journal of Physiology·A G KováchM Reivich
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·L R SquireM E Raichle
May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C Iadecola
Nov 1, 1984·The Journal of Clinical Investigation·S VorstrupO B Paulson
Feb 8, 1997·Lancet·L H LassenJ Olesen
Jun 12, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R P WhiteH S Markus
Mar 4, 2000·Nature Neuroscience·J B HopfingerG R Mangun
Nov 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jiongjiong WangJohn A Detre
Aug 3, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bojana StefanovicAfonso C Silva
Aug 11, 2006·Journal of Neurophysiology·Justin L VincentRandy L Buckner
Jan 24, 2007·NeuroImage·Bertrand ThirionJean-Baptiste Poline
Apr 11, 2008·Annals of the New York Academy of Sciences·Randy L BucknerDaniel L Schacter
Feb 17, 2009·Human Brain Mapping·Merideth A AddicottPaul J Laurienti
Mar 21, 2009·Nitric Oxide : Biology and Chemistry·Li Zhou, Dong-Ya Zhu
Jun 6, 2009·Current Opinion in Neurology·John A DetreHengyi Rao
Nov 10, 2009·Behavior Research Methods·Franz FaulAlbert-Georg Lang
Nov 27, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael KoenigsJordan Grafman
Mar 9, 2010·Trends in Cognitive Sciences·Marcus E Raichle
May 11, 2010·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Clifford R JackUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jul 8, 2010·Journal of Vascular Research·Noboru Toda, Tomio Okamura
Sep 8, 2010·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Joern R SteinertIan D Forsythe
Nov 12, 2010·Nature·David AttwellEric A Newman
Jan 3, 2012·NeuroImage·Prantik KunduPeter A Bandettini
Apr 10, 2014·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·David C AlsopGreg Zaharchuk
Jun 3, 2014·Free Radical Biology & Medicine·Cátia F LourençoJoão Laranjinha
Jun 19, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Duncan J HodkinsonSteven C R Williams
Sep 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Olivia A ShiptonMichael M Kohl
Nov 28, 2015·Magnetic Resonance Imaging·Virginia Mato AbadFernando Zelaya
Mar 8, 2017·Hypertension·Husain ShabeehAjay M Shah
Jun 25, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Sitara G KhanAjay M Shah

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