{"id":"https://openalex.org/W6983434044","doi":null,"title":"Metabolic Modulator Effects of Inorganic Nitrate and Nitrite, and Therapeutic Potential in Patients with Chronic Heart Failure","display_name":"Metabolic Modulator Effects of Inorganic Nitrate and Nitrite, and Therapeutic Potential in Patients with Chronic Heart Failure","publication_year":2020,"publication_date":"2020-12-01","ids":{"openalex":"https://openalex.org/W6983434044"},"language":"en","primary_location":{"id":"pmh:oai:ueaeprints.uea.ac.uk:82460","doi":null,"is_oa":false,"landing_page_url":"https://ueaeprints.uea.ac.uk/id/eprint/82460/1/PhD%20Thesis_B%20Loudon%20100139640.pdf","pdf_url":"https://ueaeprints.uea.ac.uk/id/eprint/82460/1/PhD%20Thesis_B%20Loudon%20100139640.pdf","source":{"id":"https://openalex.org/S4306400384","display_name":"UEA Digital Repository (University of East Anglia)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1118541","host_organization_name":"University of East Anglia","host_organization_lineage":["https://openalex.org/I1118541"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"","raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5087654045","display_name":"Brodie L. Loudon","orcid":"https://orcid.org/0009-0005-2957-7334","observed_orcids":["https://orcid.org/0009-0005-2957-7334"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Loudon, Brodie","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5087654045"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":true,"primary_topic":{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10821","display_name":"Cardiovascular Function and Risk Factors","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10924","display_name":"Cardiovascular Health and Disease Prevention","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/2705","display_name":"Cardiology and Cardiovascular Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/inorganic-nitrate","display_name":"inorganic nitrate","score":0.9190000295639038},{"id":"https://openalex.org/keywords/inorganic-nitrite","display_name":"inorganic nitrite","score":0.9330000281333923},{"id":"https://openalex.org/keywords/nitric-oxide","display_name":"nitric oxide","score":0.7670000195503235},{"id":"https://openalex.org/keywords/nitrate-nitrite-no-pathway","display_name":"nitrate-nitrite-NO pathway","score":0.9259999990463257},{"id":"https://openalex.org/keywords/chronic-heart-failure","display_name":"chronic heart failure","score":0.906000018119812},{"id":"https://openalex.org/keywords/myocardial-metabolism","display_name":"myocardial metabolism","score":0.8500000238418579},{"id":"https://openalex.org/keywords/pyruvate-dehydrogenase","display_name":"pyruvate dehydrogenase","score":0.9929999709129333},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.6430000066757202},{"id":"https://openalex.org/keywords/inflammation","display_name":"inflammation","score":0.9380000233650208},{"id":"https://openalex.org/keywords/type-2-diabetes","display_name":"type 2 diabetes","score":0.9520000219345093},{"id":"https://openalex.org/keywords/warburg-effect","display_name":"Warburg effect","score":0.7730000019073486},{"id":"https://openalex.org/keywords/aerobic-glycolysis","display_name":"aerobic glycolysis","score":0.9890000224113464},{"id":"https://openalex.org/keywords/renal-cell-carcinoma","display_name":"renal cell carcinoma","score":0.9520000219345093},{"id":"https://openalex.org/keywords/chemoresistance","display_name":"chemoresistance","score":0.6790000200271606}],"concepts":[{"id":"https://openalex.org/C2776179834","wikidata":"https://www.wikidata.org/wiki/Q72158415","display_name":"Nitrite","level":3,"score":0.6958000063896179},{"id":"https://openalex.org/C519581460","wikidata":"https://www.wikidata.org/wiki/Q207843","display_name":"Nitric oxide","level":2,"score":0.6837000250816345},{"id":"https://openalex.org/C2776384668","wikidata":"https://www.wikidata.org/wiki/Q182168","display_name":"Nitrate","level":2,"score":0.5303999781608582},{"id":"https://openalex.org/C2779395532","wikidata":"https://www.wikidata.org/wiki/Q7916469","display_name":"Vascular smooth muscle","level":3,"score":0.49950000643730164},{"id":"https://openalex.org/C2778198053","wikidata":"https://www.wikidata.org/wiki/Q181754","display_name":"Heart failure","level":2,"score":0.47679999470710754},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4652000069618225},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.45879998803138733},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4578999876976013},{"id":"https://openalex.org/C2780940725","wikidata":"https://www.wikidata.org/wiki/Q206280","display_name":"Pulmonary artery","level":2,"score":0.45730000734329224},{"id":"https://openalex.org/C2780930700","wikidata":"https://www.wikidata.org/wiki/Q1128595","display_name":"Pulmonary hypertension","level":2,"score":0.4230000078678131},{"id":"https://openalex.org/C84393581","wikidata":"https://www.wikidata.org/wiki/Q82642","display_name":"Blood pressure","level":2,"score":0.41909998655319214},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.4187999963760376},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.39809998869895935},{"id":"https://openalex.org/C48349386","wikidata":"https://www.wikidata.org/wiki/Q424361","display_name":"Reactive oxygen species","level":2,"score":0.3564000129699707},{"id":"https://openalex.org/C2776825266","wikidata":"https://www.wikidata.org/wiki/Q1410794","display_name":"Fibrinolysis","level":2,"score":0.3441999852657318},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3434000015258789},{"id":"https://openalex.org/C7836513","wikidata":"https://www.wikidata.org/wiki/Q1641506","display_name":"Hypoxia (environmental)","level":3,"score":0.3402999937534332},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3384000062942505},{"id":"https://openalex.org/C2779525624","wikidata":"https://www.wikidata.org/wiki/Q225595","display_name":"Reactive nitrogen species","level":3,"score":0.3361000120639801},{"id":"https://openalex.org/C2776820930","wikidata":"https://www.wikidata.org/wiki/Q9655","display_name":"Artery","level":2,"score":0.3343000113964081},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.33390000462532043},{"id":"https://openalex.org/C89560881","wikidata":"https://www.wikidata.org/wiki/Q101026","display_name":"Platelet","level":2,"score":0.3181999921798706},{"id":"https://openalex.org/C2776992346","wikidata":"https://www.wikidata.org/wiki/Q111140","display_name":"Endothelium","level":2,"score":0.31290000677108765},{"id":"https://openalex.org/C2777663904","wikidata":"https://www.wikidata.org/wiki/Q988343","display_name":"Blood vessel","level":2,"score":0.30889999866485596},{"id":"https://openalex.org/C120770815","wikidata":"https://www.wikidata.org/wiki/Q14859627","display_name":"Vasodilation","level":2,"score":0.30640000104904175},{"id":"https://openalex.org/C164705383","wikidata":"https://www.wikidata.org/wiki/Q10379","display_name":"Cardiology","level":1,"score":0.2824000120162964},{"id":"https://openalex.org/C2781362458","wikidata":"https://www.wikidata.org/wiki/Q1588755","display_name":"Thrombus","level":2,"score":0.28200000524520874},{"id":"https://openalex.org/C57600042","wikidata":"https://www.wikidata.org/wiki/Q227564","display_name":"Oxidative phosphorylation","level":2,"score":0.2775999903678894},{"id":"https://openalex.org/C3018697912","wikidata":"https://www.wikidata.org/wiki/Q179217","display_name":"Platelet activation","level":3,"score":0.2678000032901764},{"id":"https://openalex.org/C20251656","wikidata":"https://www.wikidata.org/wiki/Q162643","display_name":"Glycolysis","level":3,"score":0.26109999418258667},{"id":"https://openalex.org/C2777622882","wikidata":"https://www.wikidata.org/wiki/Q417619","display_name":"Nitric oxide synthase","level":3,"score":0.258899986743927},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.25760000944137573},{"id":"https://openalex.org/C1621761","wikidata":"https://www.wikidata.org/wiki/Q7997549","display_name":"Whole blood","level":2,"score":0.2531000077724457},{"id":"https://openalex.org/C541997718","wikidata":"https://www.wikidata.org/wiki/Q188151","display_name":"Ischemia","level":2,"score":0.25209999084472656},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.2513999938964844}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:ueaeprints.uea.ac.uk:82460","doi":null,"is_oa":false,"landing_page_url":"https://ueaeprints.uea.ac.uk/id/eprint/82460/1/PhD%20Thesis_B%20Loudon%20100139640.pdf","pdf_url":"https://ueaeprints.uea.ac.uk/id/eprint/82460/1/PhD%20Thesis_B%20Loudon%20100139640.pdf","source":{"id":"https://openalex.org/S4306400384","display_name":"UEA Digital Repository (University of East Anglia)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1118541","host_organization_name":"University of East Anglia","host_organization_lineage":["https://openalex.org/I1118541"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"","raw_type":"Thesis"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9391000270843506,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2168817383","https://openalex.org/W1915244501","https://openalex.org/W2742980597","https://openalex.org/W7097201714","https://openalex.org/W2566304849","https://openalex.org/W2094190834","https://openalex.org/W7218194321","https://openalex.org/W3186947443","https://openalex.org/W1966380232","https://openalex.org/W2997766552"],"abstract_inverted_index":{"Nitric":[0],"oxide":[1],"(NO)":[2],"is":[3,95,261,324,627,689],"a":[4,114,131,144,188,247,254,301,330,394,491,499,512,581,657,669,693],"crucial":[5],"signalling":[6],"molecule":[7],"within":[8,74,90],"almost":[9],"all":[10],"aspects":[11],"of":[12,69,116,125,135,154,164,170,180,184,192,268,304,317,361,404,436,441,464,493,584,668,672,684],"human":[13,216,283],"physiology.":[14],"In":[15,143],"the":[16,39,75,91,123,138,162,167,178,181,264,289,314,340,402,447,476,482,505,508,516,520,528,542,551,555,618,631,664,682],"cardiovascular":[17,139,603],"system,":[18,140],"NO":[19,70,87,105,136,298,427],"reduces":[20],"blood":[21,43],"pressure":[22],"and":[23,41,46,59,128,176,196,328,343,380,429,439,469,472,511,519,537,554,607,622,645,648,681],"vascular":[24,51],"tone,":[25],"prevents":[26,32,42],"thrombus":[27],"formation":[28,179],"via":[29,108,297,300,385,600],"platelet":[30],"activation/aggregation,":[31],"inflammation":[33,197],"by":[34,49,481,565,570],"impairing":[35,50],"leukocyte":[36],"adherence":[37],"to":[38,65,121,293,326,349,400,449,534,550,691],"endothelium,":[40],"vessel":[44],"thickening":[45],"pulmonary":[47],"hypertension":[48],"smooth":[52],"muscle":[53],"cell":[54,320,356],"proliferation.":[55],"Inorganic":[56],"nitrate":[57,127,157,408,517,552],"(NO3)":[58],"nitrite":[60,129,165,229,292,311,352,412,445,673,688],"(NO2)":[61],"were":[62],"historically":[63],"considered":[64,580],"be":[66,692],"inert":[67],"byproducts":[68],"metabolism":[71,432],"(i.e.":[72,107],"oxidation":[73],"tissues).":[76],"The":[77,525],"recently":[78],"characterised":[79],"nitrate-nitrite-NO":[80],"pathway":[81],"however,":[82],"has":[83],"revealed":[84],"an":[85],"important":[86],"storage":[88],"pool":[89],"body":[92],"that,":[93],"importantly,":[94],"highly":[96],"active":[97],"in":[98,137,148,215,241,250,257,280,417,501,504,515,527,546,557,572,610,635,651,661,674,697],"hypoxic":[99],"tissues":[100],"where":[101],"typical":[102],"mechanisms":[103],"for":[104,240,291,630],"production":[106],"Larginine)":[109],"are":[110,433],"impaired.":[111],"\\n":[112,286,287,390,563],"\\nIn":[113],"series":[115],"studies":[117],"we":[118,160,307,591],"have":[119,200,366,382,446],"sought":[120],"explore":[122,161,212],"effects":[124,163,202,206,214,267,368,386,457],"inorganic":[126,156,406],"on":[130,166,177,369,387,414,458],"less":[132],"explored":[133],"effect":[134,303,403],"cardiac":[141,217,431,459,596,642],"metabolism.":[142],"basic":[145],"science":[146],"study":[147,477,483],"mice":[149],"supplemented":[150],"with":[151,243,263,419,422,444,485,574,587,613,617,677],"7":[152],"days":[153],"oral":[155,405],"or":[158,282,299,371,378],"nitrite,":[159],"rate-limiting":[168],"enzyme":[169],"glucose":[171,468],"metabolism,":[172,295],"pyruvate":[173],"dehydrogenase":[174],"(PDH),":[175],"oxidative":[182,334],"dimer":[183,232,258],"protein":[185],"kinase":[186],"G-1\u03b1,":[187],"newly-characterised":[189],"downstream":[190],"transducer":[191],"reactive":[193],"oxygen":[194],"species":[195],"that":[198,626],"may":[199,381],"beneficial":[201],"acutely":[203],"but":[204,274,363],"detrimental":[205],"if":[207],"chronically":[208],"activated.":[209],"We":[210,637],"also":[211,271,308,383,392],"these":[213,442,698],"biopsy":[218],"samples":[219],"obtained":[220,569],"from":[221,333,490],"patients":[222,242,418,488,573],"undergoing":[223],"coronary":[224],"artery":[225],"bypass":[226],"surgery.":[227],"Although":[228],"increased":[230],"PKG1\u03b1":[231],"content,":[233],"this":[234,345,547],"was":[235,253,478,522,531,615],"not":[236,276,365],"statistically":[237,523],"significant,":[238],"except":[239],"type":[244],"2":[245],"diabetes,":[246],"pro-inflammatory":[248],"state,":[249],"whom":[251],"there":[252],"robust":[255],"reduction":[256],"formation.":[259],"This":[260],"in-keeping":[262],"known":[265],"anti-inflammatory":[266],"nitrite.":[269],"Nitrite":[270],"dephosphorylated":[272],"PDH":[273,370],"did":[275,364],"increase":[277,347,410,514],"its":[278,305],"activity":[279],"mouse":[281],"heart":[284,420,437,539,585,675],"tissue.":[285],"\\nGiven":[288],"potential":[290,448,456],"affect":[294,313],"either":[296],"direct":[302],"own,":[306],"investigated":[309],"whether":[310,344,593],"could":[312],"metabolic":[315,373,702],"profile":[316],"786-0":[318],"renal":[319],"carcinoma":[321],"cells,":[322],"which":[323],"unique":[325,582],"cancers":[327],"involves":[329],"switch":[331],"away":[332],"phosphorylation":[335],"towards":[336],"aerobic":[337],"glycolysis":[338],"(termed":[339],"Warburg":[341],"effect),":[342],"might":[346],"susceptibility":[348],"chemotherapy.":[350],"Interestingly,":[351],"slightly":[353],"improved":[354],"cancer":[355],"survival":[357],"at":[358],"lower":[359],"doses":[360],"chemotherapy,":[362],"any":[367],"other":[372,686,701],"proteins":[374],"such":[375,560],"as":[376,453,455,561,656],"Akt":[377],"LDH,":[379],"occurred":[384],"redox":[388],"signalling.":[389],"\\nWe":[391],"designed":[393],"large,":[395],"randomised":[396],"controlled":[397],"clinical":[398],"trial":[399,671],"investigate":[401],"(sodium)":[407],"(to":[409],"plasma":[411],"levels)":[413],"exercise":[415,451,502,633,646],"capacity":[416],"failure":[421,540,586,676],"reduced":[423,430],"ejection":[424,589,679],"fraction.":[425],"Inflammation,":[426],"deficiency,":[428],"key":[434,658],"features":[435,443],"failure,":[438],"correction":[440],"improve":[450],"tolerance,":[452],"well":[454],"function,":[460],"serum":[461,467],"biomarkers,":[462],"quality":[463],"life":[465],"score,":[466],"insulin":[470],"levels,":[471],"inflammatory":[473],"markers.":[474],"Unfortunately,":[475],"halted":[479],"prematurely":[480],"Sponsor,":[484],"only":[486],"19":[487],"recruited":[489],"target":[492,660],"56.":[494],"However,":[495],"our":[496,685],"results":[497,667,683],"showed":[498],"fall":[500,526],"tolerance":[503],"group":[506,530],"receiving":[507],"placebo":[509,529],"medication,":[510],"small":[513],"arm,":[518,553],"difference":[521],"significant.":[524],"likely":[532],"due":[533],"disease":[535],"progression":[536],"worsening":[538],"given":[541],"better":[543],"baseline":[544],"function":[545],"arm":[548],"compared":[549],"change":[556,609],"echocardiographic":[558],"data":[559,567],"V100.":[562],"\\nFinally,":[564],"analysing":[566],"previously":[568],"others":[571],"symptomatic":[575],"non-obstructive":[576],"hypertrophic":[577],"cardiomyopathy":[578],"(often":[579],"subphenotype":[583],"preserved":[588,678],"fraction),":[590],"assessed":[592],"impaired":[594,623],"resting":[595,601],"energetic":[597,643,654],"status":[598],"(measured":[599],"31P":[602],"magnetic":[604],"resonance":[605],"spectroscopy":[606],"dynamic":[608,619],"vasculoventricular":[611,649],"coupling":[612,650],"exercise)":[614],"associated":[616],"diastolic":[620],"dysfunction":[621],"Frank-Starling":[624],"mechanism":[625],"largely":[628],"responsible":[629],"profound":[632],"intolerance":[634,647],"HCM.":[636,662],"demonstrate":[638],"modest":[639],"correlations":[640],"between":[641],"impairment":[644,655],"HCM,":[652],"identifying":[653],"therapeutic":[659],"Given":[663],"recent":[665],"equivocal":[666],"definitive":[670],"fraction,":[680],"studies,":[687],"unlikely":[690],"clinically":[694],"useful":[695],"treatment":[696],"patients,":[699],"however":[700],"modulators":[703],"remain":[704],"attractive.":[705]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2025-10-10T00:00:00"}