2023
Bradykinin B2 receptor blockade and intradialytic hypotension
Gamboa J, Mambungu C, Clagett A, Nian H, Yu C, Ikizler T, Brown N. Bradykinin B2 receptor blockade and intradialytic hypotension. BMC Nephrology 2023, 24: 134. PMID: 37170244, PMCID: PMC10176680, DOI: 10.1186/s12882-023-03192-4.Peer-Reviewed Original ResearchConceptsBradykinin B2 receptor blockadeB2 receptor blockadeMaintenance hemodialysisBlood pressureReceptor blockersReceptor blockadeIntradialytic hypotensionBradykinin B2 receptor blockerLack of vasoconstrictionProduction of vasodilatorsSystolic blood pressureGroup of patientsCrossover clinical trialCommon clinical complicationHemodynamic effectsClinical complicationsContinuous infusionClinical trialsStratified analysisIcatibantHemodialysisPatientsHypotensionPlaceboCompensatory mechanisms
2018
Endogenous bradykinin and B1-B5 during angiotensin-converting enzyme inhibitor–associated angioedema
Hubers S, Kohm K, Wei S, Yu C, Nian H, Grabert R, Sexton DJ, Brown NJ. Endogenous bradykinin and B1-B5 during angiotensin-converting enzyme inhibitor–associated angioedema. Journal Of Allergy And Clinical Immunology 2018, 142: 1636-1639.e5. PMID: 30036596, PMCID: PMC6226317, DOI: 10.1016/j.jaci.2018.06.037.Peer-Reviewed Original Research
2017
Angiotensin-converting Enzyme Inhibitor and Other Drug-associated Angioedema
Stone C, Brown NJ. Angiotensin-converting Enzyme Inhibitor and Other Drug-associated Angioedema. Immunology And Allergy Clinics Of North America 2017, 37: 483-495. PMID: 28687104, DOI: 10.1016/j.iac.2017.04.006.Peer-Reviewed Original ResearchConceptsDrug-induced angioedemaEnzyme inhibitorsAngiotensin-converting enzyme inhibitorNon-β-lactam antibioticsNonsteroidal antiinflammatory agentsNonallergic angioedemaSubstance PTherapeutic decisionsAngioedemaAntiinflammatory agentsLactam antibioticsOther DrugΒ-lactam antibioticsDrugsPatientsLeukotrienesBradykininGenetic variantsAntibioticsInhibitorsAngiotensinProstaglandinsAgentsHistamineMainstay
2016
Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema
Straka BT, Ramirez CE, Byrd JB, Stone E, Woodard-Grice A, Nian H, Yu C, Banerji A, Brown NJ. Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema. Journal Of Allergy And Clinical Immunology 2016, 140: 242-248.e2. PMID: 27913306, PMCID: PMC5705179, DOI: 10.1016/j.jaci.2016.09.051.Peer-Reviewed Original ResearchConceptsACE inhibitor-associated angioedemaResolution of symptomsVisual analog scaleAnalog scaleReceptor antagonistTreatment groupsBradykinin BEnzyme (ACE) inhibitor-associated angioedemaStudy drug administrationReceptor antagonist icatibantHours of presentationTreatment of attacksC1 inhibitor deficiencyBradykinin receptor antagonismFrequency of administrationVanderbilt University Medical CenterUniversity Medical CenterMassachusetts General HospitalTwo-thirdsAntagonist icatibantBowel edemaWhite patientsH2 blockersClinical efficacyInhibitor deficiencyCombined Angiotensin Receptor Antagonism and Neprilysin Inhibition
Hubers SA, Brown NJ. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition. Circulation 2016, 133: 1115-1124. PMID: 26976916, PMCID: PMC4800749, DOI: 10.1161/circulationaha.115.018622.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, Drug-InducedAminobutyratesAngioedemaAngiotensin Receptor AntagonistsBiphenyl CompoundsBradykininContraindicationsDrug CombinationsDrug CostsDrug SynergismEnalaprilEnzyme InhibitorsFemaleFollow-Up StudiesHeart FailureHumansHyperkalemiaHypertensionKidneyMulticenter Studies as TopicNatriuretic PeptidesNeprilysinPregnancyProdrugsProspective StudiesPyridinesRandomized Controlled Trials as TopicStroke VolumeTetrazolesThiazepinesValsartanConceptsValsartan/sacubitrilReduced ejection fractionHeart failureNatriuretic peptideEjection fractionN-terminal pro-brain natriuretic peptideNeprilysin inhibitor prodrug sacubitrilPro-brain natriuretic peptideAngiotensin receptor blocker valsartanAngiotensin receptor antagonismAngiotensin receptor blockersHeart Failure TrialReceptor blocker valsartanAngiotensin receptor antagonistsBrain natriuretic peptideOngoing clinical trialsMechanism of actionNeprilysin inhibitionAldosterone antagonistsAldosterone systemReceptor blockersBlood pressureFailure TrialPathophysiological mechanismsReceptor antagonism
2015
Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis – a randomized cross-over study
Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis – a randomized cross-over study. BMC Nephrology 2015, 16: 167. PMID: 26494370, PMCID: PMC4618919, DOI: 10.1186/s12882-015-0162-x.Peer-Reviewed Original ResearchConceptsEnd-stage renal diseaseAngiotensin receptor blockersMaintenance hemodialysisCross-over studyADMA levelsAsymmetric dimethylarginineACE inhibitionADMA productionADMA concentrationsShort-term ACE inhibitionRandomized cross-over studyIntracellular ADMA concentrationStudy of patientsEffect of bradykininB2 receptor stimulationACE inhibitor-induced increaseInhibitor-induced increaseRamipril treatmentCardiovascular morbidityReceptor blockersEndothelial dysfunctionRenal diseaseBradykinin levelsBackgroundEndothelial dysfunctionDialysis session
2014
Substance P Increases Sympathetic Activity During Combined Angiotensin-Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition
Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ. Substance P Increases Sympathetic Activity During Combined Angiotensin-Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition. Hypertension 2014, 63: 951-957. PMID: 24516103, PMCID: PMC3984385, DOI: 10.1161/hypertensionaha.113.02767.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininCross-Over StudiesDipeptidyl Peptidase 4Double-Blind MethodEnalaprilatEnzyme InhibitorsFemaleHeart RateHumansMaleMiddle AgedNeurotransmitter AgentsNorepinephrinePeptidyl-Dipeptidase APyrazinesSitagliptin PhosphateSubstance PSympathetic Nervous SystemTriazolesVascular ResistanceConceptsDipeptidyl peptidase-4 inhibitionPeptidase-4 inhibitionTissue plasminogen activator releaseSubstance PDipeptidyl peptidase-4Plasminogen activator releaseSympathetic activityPeptidase-4Activator releasePlacebo-controlled crossover studyDipeptidyl peptidase-4 inhibitorsType 2 diabetes mellitusIntra-arterial enalaprilatForearm vascular resistanceForearm blood flowMean arterial pressurePeptidase-4 inhibitorsAngiotensin converting enzymeSubstrates of angiotensinVascular resistanceVasodilator responseArterial pressureBrachial arteryDiabetes mellitusCrossover study
2012
Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial
Balaguer JM, Yu C, Byrne JG, Ball SK, Petracek MR, Brown NJ, Pretorius M. Contribution of Endogenous Bradykinin to Fibrinolysis, Inflammation, and Blood Product Transfusion Following Cardiac Surgery: A Randomized Clinical Trial. Clinical Pharmacology & Therapeutics 2012, 93: 326-334. PMID: 23361105, PMCID: PMC4031681, DOI: 10.1038/clpt.2012.249.Peer-Reviewed Original ResearchConceptsBradykinin B2 receptor antagonismB2 receptor antagonismCardiopulmonary bypassEndogenous bradykininTissue-type plasminogen activatorHoe 140Receptor antagonismBradykinin B2 receptor antagonistSubsequent transfusion requirementsBlood product transfusionProportion of patientsB2 receptor antagonistD-dimer concentrationD-dimer formationEACA treatmentTransfusion requirementsPostoperative bleedingProduct transfusionBlood lossCardiac surgeryInflammatory cytokinesReceptor antagonistClinical trialsFibrinolytic capacityInflammatory responsePolymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans
Marczak ED, Marzec J, Zeldin DC, Kleeberger SR, Brown NJ, Pretorius M, Lee CR. Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. Pharmacogenetics And Genomics 2012, 22: 620-628. PMID: 22668754, PMCID: PMC3599320, DOI: 10.1097/fpc.0b013e32835516e5.Peer-Reviewed Original ResearchConceptsForearm vascular resistanceForearm blood flowVariant allele carriersVasodilator responseSodium nitroprussideVascular functionAllele carriersStrain-gauge venous occlusion plethysmographyLower forearm blood flowEndothelial-independent mannerForearm vasodilator responseVenous occlusion plethysmographyWild-type individualsTranscription factor Nrf2Endothelial dysfunctionOcclusion plethysmographyVascular resistanceIncremental dosesCardiovascular diseaseBlood flowG genotypeA polymorphismSignificant associationBasal conditionsFactor Nrf2Comparative Effects of Angiotensin Receptor Blockade and ACE Inhibition on the Fibrinolytic and Inflammatory Responses to Cardiopulmonary Bypass
Billings F, Balaguer J, Yu C, Wright P, Petracek M, Byrne J, Brown N, Pretorius M. Comparative Effects of Angiotensin Receptor Blockade and ACE Inhibition on the Fibrinolytic and Inflammatory Responses to Cardiopulmonary Bypass. Clinical Pharmacology & Therapeutics 2012, 91: 1065-1073. PMID: 22549281, PMCID: PMC3822756, DOI: 10.1038/clpt.2011.356.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsBenzimidazolesBiphenyl CompoundsBlood TransfusionBradykininCardiopulmonary BypassEndpoint DeterminationFemaleFibrinolysisHematocritHospital MortalityHumansInflammationInterleukinsLength of StayMaleMiddle AgedMonitoring, IntraoperativePerioperative CarePostoperative ComplicationsRamiprilTetrazolesTreatment OutcomeConceptsAngiotensin II type 1 receptor blockadeACE inhibitionCardiopulmonary bypassReceptor blockadeInflammatory responseType 1 receptor blockadeTissue-type plasminogen activator concentrationAngiotensin receptor blockadeEffect of angiotensinRed cell transfusionDay of surgeryPlasminogen activator inhibitor-1Activator inhibitor-1Plasminogen activator concentrationsHospital stayPlasma transfusionIL-10ACE inhibitorsIL-8Intraoperative fibrinolysisFibrinolysisInhibitor-1Comparative effectsPlaceboTransfusion
2010
Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans
Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans. Hypertension 2010, 57: 116-122. PMID: 21098312, PMCID: PMC3020911, DOI: 10.1161/hypertensionaha.110.161695.Peer-Reviewed Original ResearchConceptsForearm blood flowVariant allele carriersForearm vasodilator responseForearm vascular resistanceSoluble epoxide hydrolaseVascular resistanceVasodilator responseBlood flowAllele carriersSodium nitroprussideVascular functionStrain-gauge venous occlusion plethysmographyHighest forearm blood flowLower forearm vascular resistanceSignificant associationCytochrome P450-derived epoxyeicosatrienoic acidsEpoxide hydrolaseVenous occlusion plethysmographyCardiovascular disease riskEndothelium-independent mannerWild-type individualsOcclusion plethysmographyPotent vasodilatorEpoxyeicosatrienoic acidsPreclinical modelsBradykinin forming capacity of oversulfated chondroitin sulfate contaminated heparin in vitro
Adam A, Montpas N, Keire D, Désormeaux A, Brown NJ, Marceau F, Westenberger B. Bradykinin forming capacity of oversulfated chondroitin sulfate contaminated heparin in vitro. Biomaterials 2010, 31: 5741-5748. PMID: 20427081, PMCID: PMC2896062, DOI: 10.1016/j.biomaterials.2010.03.074.Peer-Reviewed Original ResearchConceptsContact system activationAnaphylactoid reactionsOversulfated chondroitin sulfateSystem activationSevere anaphylactoid reactionPlasma contact systemHuman plasmaInflammatory peptidesChondroitin sulfateEnzyme inhibitorsBK releaseDrug AdministrationBradykininHeparinSignificant correlationDefinitive evidenceDextran sulfatePlasma dilutionActivationConclusionPatientsPathophysiologyKininsAdministrationPlasmaIncreased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism
Fong P, Stafforini DM, Brown NJ, Pretorius M. Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism. Free Radical Biology And Medicine 2010, 49: 301-305. PMID: 20423727, PMCID: PMC2916026, DOI: 10.1016/j.freeradbiomed.2010.04.023.Peer-Reviewed Original ResearchConceptsForearm blood flowHypertensive subjectsL-NMMAIsoprostane releaseBlood flowOxidative stressBasal forearm blood flowNitric oxide-independent mechanismEndothelium-independent mechanismNO synthase inhibitorEffect of bradykininMonomethyl-L-arginineIntraarterial bradykininPotent vasodilatorSynthase inhibitionSynthase inhibitorBradykininNitric oxideDependent mechanismReactive oxygen speciesHuman vasculatureSignificant increaseNitroprussideSubjectsOxygen species
2009
Endogenous Nitric Oxide Contributes to Bradykinin-Stimulated Glucose Uptake but Attenuates Vascular Tissue-Type Plasminogen Activator Release
Pretorius M, Brown NJ. Endogenous Nitric Oxide Contributes to Bradykinin-Stimulated Glucose Uptake but Attenuates Vascular Tissue-Type Plasminogen Activator Release. Journal Of Pharmacology And Experimental Therapeutics 2009, 332: 291-297. PMID: 19841473, PMCID: PMC2802470, DOI: 10.1124/jpet.109.160168.Peer-Reviewed Original ResearchConceptsT-PA releaseNet t-PA releaseForearm blood flowTissue-type plasminogen activator releaseL-NMMANitric oxide synthasePlasminogen activator releaseGlucose uptakeActivator releaseBaseline forearm blood flowBaseline forearm vascular resistanceArterial-venous gradientEndogenous NO contributesForearm vascular resistanceNitric oxide contributesIntra-arterial bradykininMonomethyl-L-arginineMuscle glucose uptakeCyclooxygenase inhibitor aspirinEndogenous nitric oxide contributesGender-stratified analysesVascular resistanceNondiabetic subjectsNOS inhibitionFibrinolytic responseEndogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis
Marney AM, Ma J, Luther JM, Ikizler TA, Brown NJ. Endogenous Bradykinin Contributes to Increased Plasminogen Activator Inhibitor 1 Antigen following Hemodialysis. Journal Of The American Society Of Nephrology 2009, 20: 2246-2252. PMID: 19628666, PMCID: PMC2754101, DOI: 10.1681/asn.2009050505.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1 antigenHoe 140Endogenous bradykininHemodialysis patientsMCP-1Receptor blocker HOE-140Placebo-controlled crossover studyOxidative stressChronic hemodialysis patientsMean arterial pressureCoronary artery diseaseKallikrein-kinin systemBradykinin receptor antagonismHeart rate responsePAI-1 antigenTissue plasminogen activatorEffect of dialysisEnd of dialysisProduction of bradykininInhibits platelet aggregationCardiovascular eventsHemodialysis populationArterial pressureArtery diseaseEndothelial release
2008
17&bgr;-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women
Pretorius M, van Guilder GP, Guzman RJ, Luther JM, Brown NJ. 17&bgr;-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women. Hypertension 2008, 51: 1190-1196. PMID: 18259028, PMCID: PMC2673569, DOI: 10.1161/hypertensionaha.107.105627.Peer-Reviewed Original ResearchConceptsYounger postmenopausal womenT-PA antigenEffect of angiotensinPostmenopausal womenT-PA releaseActive t-PAT-PAAntigen releasePlasminogen activator inhibitor-1 antigenTissue-type plasminogen activator releaseNet t-PA releaseForearm blood flowPlasminogen activator releaseEnzyme inhibitionCrossover studyIntraarterial infusionBasal releaseVascular releaseTreatment periodFibrinolytic functionPlaceboBlood flowActivator releaseAngiotensinAntigenBradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition
Van Guilder GP, Pretorius M, Luther JM, Byrd JB, Hill K, Gainer JV, Brown NJ. Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition. Hypertension 2008, 51: 454-459. PMID: 18180402, PMCID: PMC2581632, DOI: 10.1161/hypertensionaha.107.102574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininDrug SynergismEnalaprilatEndothelium, VascularFemaleForearmGenotypeHumansInjections, Intra-ArterialMaleMethacholine ChlorideNitroprussidePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowSex FactorsTissue Plasminogen ActivatorVascular ResistanceVasodilationVasodilator AgentsConceptsForearm blood flowT-PA releaseForearm vascular resistanceVascular resistanceBlood flowBlood pressureTissue-type plasminogen activator releaseBasal forearm blood flowAngiotensin-Converting Enzyme InhibitionGenotype groupsNet t-PA releaseReceptor-mediated vasodilationBasal forearm vascular resistanceSystolic blood pressureBody mass indexIntra-arterial bradykininEffect of bradykininDegradation of bradykininPlasminogen activator releaseEnzyme inhibitionMass indexVascular responsesActivator releaseBradykininWhite American subjects
2007
Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema
Byrd JB, Touzin K, Sile S, Gainer JV, Yu C, Nadeau J, Adam A, Brown NJ. Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema. Hypertension 2007, 51: 141-147. PMID: 18025295, PMCID: PMC2749928, DOI: 10.1161/hypertensionaha.107.096552.Peer-Reviewed Original ResearchConceptsEnzyme (ACE) inhibitor-associated angioedemaDipeptidyl peptidase IV activityHistory of angiotensinPeptidase IV activityControl subjectsSubstance PDipeptidyl peptidase IVEnzyme inhibitorsLife-threatening adverse effectsAngiotensin converting enzyme (ACE) inhibitorsEnzyme inhibitionAbsence of angiotensinPrevalence of smokingSera of patientsCase-control studyPeptidase IVSubstrates of angiotensinTissue edemaAssociated angioedemaAminopeptidase P activityVascular permeabilityAngioedemaAngiotensinAminopeptidase N activityAmino-terminal degradationThe Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance
Pretorius MM, Gainer JV, Van Guilder GP, Coelho EB, Luther JM, Fong P, Rosenbaum DD, Malave HA, Yu C, Ritchie MD, Vaughan DE, Brown NJ. The Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance. Clinical Pharmacology & Therapeutics 2007, 83: 122-129. PMID: 17522594, DOI: 10.1038/sj.clpt.6100250.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanBlood Flow VelocityBlood PressureBradykininDose-Response Relationship, DrugFemaleForearmGene FrequencyGenotypeHumansInfusions, Intra-ArterialMaleNitroprussidePhenotypePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowVascular ResistanceVasodilator AgentsWhite PeopleConceptsSystolic blood pressureForearm vascular resistanceVascular resistanceBlood pressureEndothelium-independent agonist sodium nitroprussideEndothelium-dependent agonist bradykininIntrabrachial artery infusionsLeft ventricular massBradykinin B2 receptor geneB2 receptor geneNormotensive subjectsVentricular massPulse pressureB2 receptorsAgonist bradykininSodium nitroprussideReceptor geneBradykininGroupPolymorphismInfusionWhite AmericansNitroprussideBaselineBlack Americans
2006
Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering during AT1 Receptor Blockade
LeFebvre J, Shintani A, Gebretsadik T, Petro JR, Murphey LJ, Brown NJ. Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering during AT1 Receptor Blockade. Journal Of Pharmacology And Experimental Therapeutics 2006, 320: 1261-1267. PMID: 17182977, DOI: 10.1124/jpet.106.117259.Peer-Reviewed Original ResearchConceptsPlasma renin activityHoe 140Endogenous bradykininReceptor blockadeBaseline plasma renin activityBlood pressure-lowering effectAT1 receptor blockadeSalt-depleted subjectsBlood pressure loweringBlood pressure responseEffect of angiotensinPressure-lowering effectAngiotensin I/Heart rate responseReceptor-independent mechanismD-Arg-ArgBradykinin B2 receptorPRA responseRenin activityChronic treatmentPlasma cGMPPressure loweringB2 receptorsEndocrine responsesHeart rate