{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:41:45Z","timestamp":1771472505987,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T00:00:00Z","timestamp":1368662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"Background and Purpose<\/jats:title>Nitrite (NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup>) has recently been shown to represent a potential source of NO<\/jats:styled-content>, in particular under hypoxic conditions. The aim of the current study was to compare the haemodynamic effects of NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> in healthy volunteers and patients with stable congestive heart failure (CHF<\/jats:styled-content>).<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>The acute haemodynamic effects of brachial artery infusion of NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> (0.31 to 7.8\u2009\u03bcmol\u00b7min\u22121<\/jats:sup>) was assessed in normal subjects (n<\/jats:italic> = 20) and CHF<\/jats:styled-content> patients (n<\/jats:italic> = 21).<\/jats:p><\/jats:sec>Key Results<\/jats:title>NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion was well tolerated in all subjects. Forearm blood flow (FBF<\/jats:styled-content>) increased markedly in CHF<\/jats:styled-content> patients at NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion rates which induced no changes in normal subjects (anova<\/jats:sc>: F<\/jats:styled-content><\/jats:italic> = 5.5; P<\/jats:italic> = 0.02). Unstressed venous volume (UVV<\/jats:styled-content>) increased even with the lowest NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion rate in all subjects (indicating venodilation), with CHF<\/jats:styled-content> patients being relatively hyporesponsive compared with normal subjects (anova<\/jats:sc>: F<\/jats:styled-content><\/jats:italic> = 6.2; P<\/jats:italic> = 0.01). There were no differences in venous blood pH<\/jats:styled-content> or oxygen concentration between groups or during NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion. Venous plasma NO<\/jats:roman><\/jats:styled-content>2<\/jats:sub>\u2212<\/jats:sup> concentrations were lower in CHF<\/jats:styled-content> patients at baseline, and rose substantially less with NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion, without incremental oxidative generation of nitrate, consistent with accelerated clearance in these patients. Plasma protein\u2010bound NO<\/jats:styled-content> concentrations were lower in CHF<\/jats:styled-content> patients than normal subjects at baseline. This difference was attenuated during NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> infusion. Prolonged NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> exposure in vivo<\/jats:italic> did not induce oxidative stress, nor did it induce tolerance in vitro<\/jats:italic>.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>The findings of arterial hyper\u2010responsiveness to infused NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> in CHF<\/jats:styled-content> patients, with evidence of accelerated transvascular NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> clearance (presumably with concomitant NO<\/jats:styled-content> release) suggests that NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> effects may be accentuated in such patients. These findings provide a stimulus for the clinical exploration of NO2<\/jats:sub><\/jats:roman><\/jats:styled-content>\u2212<\/jats:sup> as a therapeutic modality in CHF<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12152","type":"journal-article","created":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T13:20:36Z","timestamp":1362748836000},"page":"659-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite"],"prefix":"10.1111","volume":"169","author":[{"given":"Abdul R","family":"Maher","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayqa","family":"Arif","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Madhani","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Abozguia","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernadette O","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Southampton General Hospital University of Southampton Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Feelisch","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences Southampton General Hospital University of Southampton Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AG","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Sciences School of Clinical and Experimental Medicine College of Medical and Dental Sciences University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Christopoulos","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences Monash University Melbourne Vic. 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