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https://hdl.handle.net/2440/79116
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dc.contributor.author | Maher, A. | - |
dc.contributor.author | Arif, S. | - |
dc.contributor.author | Madhani, M. | - |
dc.contributor.author | Abozguia, K. | - |
dc.contributor.author | Ahmed, I. | - |
dc.contributor.author | Fernandez, B. | - |
dc.contributor.author | Feelisch, M. | - |
dc.contributor.author | O'Sullivan, A. | - |
dc.contributor.author | Christopoulos, A. | - |
dc.contributor.author | Sverdlov, A. | - |
dc.contributor.author | Ngo, D. | - |
dc.contributor.author | Dautov, R. | - |
dc.contributor.author | James, P. | - |
dc.contributor.author | Horowitz, J. | - |
dc.contributor.author | Frennaux, M. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | British Journal of Pharmacology, 2013; 169(3):659-670 | - |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.issn | 1476-5381 | - |
dc.identifier.uri | http://hdl.handle.net/2440/79116 | - |
dc.description.abstract | <h4>Background and purpose</h4>Nitrite (NO₂⁻) has recently been shown to represent a potential source of NO, in particular under hypoxic conditions. The aim of the current study was to compare the haemodynamic effects of NO₂⁻ in healthy volunteers and patients with stable congestive heart failure (CHF).<h4>Experimental approach</h4>The acute haemodynamic effects of brachial artery infusion of NO₂⁻ (0.31 to 7.8 μmol·min⁻¹) was assessed in normal subjects (n = 20) and CHF patients (n = 21).<h4>Key results</h4>NO₂⁻ infusion was well tolerated in all subjects. Forearm blood flow (FBF) increased markedly in CHF patients at NO₂⁻ infusion rates which induced no changes in normal subjects (ANOVA: F = 5.5; P = 0.02). Unstressed venous volume (UVV) increased even with the lowest NO₂⁻ infusion rate in all subjects (indicating venodilation), with CHF patients being relatively hyporesponsive compared with normal subjects (ANOVA: F = 6.2; P = 0.01). There were no differences in venous blood pH or oxygen concentration between groups or during NO₂⁻ infusion. Venous plasma NO₂⁻ concentrations were lower in CHF patients at baseline, and rose substantially less with NO₂⁻ infusion, without incremental oxidative generation of nitrate, consistent with accelerated clearance in these patients. Plasma protein-bound NO concentrations were lower in CHF patients than normal subjects at baseline. This difference was attenuated during NO₂⁻ infusion. Prolonged NO₂⁻ exposure in vivo did not induce oxidative stress, nor did it induce tolerance in vitro.<h4>Conclusions and implications</h4>The findings of arterial hyper-responsiveness to infused NO₂⁻ in CHF patients, with evidence of accelerated transvascular NO₂⁻ clearance (presumably with concomitant NO release) suggests that NO₂⁻ effects may be accentuated in such patients. These findings provide a stimulus for the clinical exploration of NO₂⁻ as a therapeutic modality in CHF. | - |
dc.description.statementofresponsibility | Abdul R Maher, Sayqa Arif, Melanie Madhani, Khalid Abozguia, Ibrar Ahmed, Bernadette O Fernandez, Martin Feelisch, AG O’Sullivan, Arthur Christopoulos, Aaron L Sverdlov, Doan Ngo, Rustem Dautov, Philip E James, John D Horowitz and Michael P Frenneaux | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2013 The Authors | - |
dc.source.uri | http://dx.doi.org/10.1111/bph.12152 | - |
dc.subject | sodium nitrite | - |
dc.subject | vascular effects | - |
dc.subject | heart failure | - |
dc.title | Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1111/bph.12152 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Sverdlov, A. [0000-0003-2539-8038] | - |
dc.identifier.orcid | Horowitz, J. [0000-0001-6883-0703] | - |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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