title: Paradoxical normoxia-dependent selective actions of inorganic nitrite in human muscular conduit arteries and related selective actions on central blood pressures.
abstract: BACKGROUND
  Inorganic nitrite dilates small resistance arterioles via hypoxia-facilitated reduction to vasodilating nitric oxide. The effects of nitrite in human conduit arteries have not been investigated. In contrast to nitrite, organic nitrates are established selective dilators of conduit arteries.
  
  
  RESULTS
  We examined the effects of local and systemic administration of sodium nitrite on the radial artery (a muscular conduit artery), forearm resistance vessels (forearm blood flow), and systemic hemodynamics in healthy male volunteers (n=43). Intrabrachial sodium nitrite (8.7 μmol/min) increased radial artery diameter by a median of 28.0% (25th and 75th percentiles, 25.7% and 40.1%; P<0.001). Nitrite (0.087-87 μmol/min) displayed conduit artery selectivity similar to that of glyceryl trinitrate (0.013-4.4 nmol/min) over resistance arterioles. Nitrite dose-dependently increased local cGMP production at the dose of 2.6 μmol/min by 1.1 pmol·min(-1)·100 mL(-1) tissue (95% confidence interval, 0.5-1.8). Nitrite-induced radial artery dilation was enhanced by administration of acetazolamide (oral or intra-arterial) and oral raloxifene (P=0.0248, P<0.0001, and P=0.0006, respectively) but was inhibited under hypoxia (P<0.0001) and hyperoxia (P=0.0006) compared with normoxia. Systemic intravenous administration of sodium nitrite (8.7 μmol/min) dilated the radial artery by 10.7% (95% confidence interval, 6.8-14.7) and reduced central systolic blood pressure by 11.6 mm Hg (95% confidence interval, 2.4-20.7), augmentation index, and pulse wave velocity without changing peripheral blood pressure.
  
  
  CONCLUSIONS
  Nitrite selectively dilates conduit arteries at supraphysiological and near-physiological concentrations via a normoxia-dependent mechanism that is associated with cGMP production and is enhanced by acetazolamide and raloxifene. The selective central blood pressure-lowering effects of nitrite have therapeutic potential to reduce cardiovascular events.
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Sami A
authors.initials: SA
authors.lastname: Omar
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: Fok
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Katharina D
authors.initials: KD
authors.lastname: Tilgner
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Ashok
authors.initials: A
authors.lastname: Nair
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hunt
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Benyu
authors.initials: B
authors.lastname: Jiang
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: Chowienczyk
authors.affiliation: From the King's College London British Heart Foundation Centre, Cardiovascular Division, Department of Clinical Pharmacology, London, UK (S.A.O., H.F., A.N., J.H., B.J., P.C., A.J.W.); Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, London, UK (K.D.T., P.T.); Department of Anaesthetics (A.N.), and Biomedical Research Centre (S.A.O., H.F., A.N., J.H., B.J., P.C., A.W.), Guy's & St. Thomas' NHS Foundation Trust, London, UK. andrew.1.webb@kcl.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D017534:Radial Artery / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D012977:Sodium Nitrite
keywords: arteries; blood pressure; nitrites; nitroglycerin; vasodilation