2022
DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment
Wilson JR, Garner EM, Mashayekhi M, Hubers SA, Bustamante C, Kerman SJ, Nian H, Shibao CA, Brown NJ. DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment. Hypertension 2022, 79: 827-835. PMID: 35045722, PMCID: PMC8917054, DOI: 10.1161/hypertensionaha.121.18348.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensinsAprepitantBlood PressureCardiovascular AgentsCatecholaminesCross-Over StudiesDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4HumansNorepinephrineRamiprilRenin-Angiotensin SystemSitagliptin PhosphateValsartanConceptsDPP4 inhibitionBlood pressureACE inhibitionDouble-blind crossover studyAcute ACE inhibitionBlood pressure armNK1 receptor blockerACE inhibitor treatmentOral diabetes medicationsCalcium channel blockersType 2 diabetesEffects of DPP4Aldosterone systemCardiovascular complicationsDiabetes medicationsReceptor blockersCardiovascular effectsCrossover therapyHeart failureHypotensive effectCrossover studyChannel blockersDPP4 inhibitorsHeart rateInhibitor treatment
2019
Dipeptidyl Peptidase 4 Inhibition Increases Postprandial Norepinephrine via Substance P (NK1 Receptor) During RAAS Inhibition
Wilson JR, Kerman SJ, Hubers SA, Yu C, Nian H, Grouzmann E, Eugster PJ, Mayfield DS, Brown NJ. Dipeptidyl Peptidase 4 Inhibition Increases Postprandial Norepinephrine via Substance P (NK1 Receptor) During RAAS Inhibition. Journal Of The Endocrine Society 2019, 3: 1784-1798. PMID: 31528826, PMCID: PMC6734191, DOI: 10.1210/js.2019-00185.Peer-Reviewed Original ResearchPostprandial blood pressureDPP4 inhibitionNPY 1Blood pressureHeart failureACE inhibitionSubstance PVasoactive peptidesPostprandial glucagon-like peptide-1Substance P receptor blockadeDipeptidyl peptidase-4 inhibitorsGlucagon-like peptide-1Mixed-meal studyAngiotensin receptor blockersDouble-blind treatmentPeptidase-4 inhibitorsType 2 diabetesReceptor-dependent mechanismAntihypertensive groupNPY 3Y1 agonistRAAS inhibitionReceptor blockersReceptor blockadeACE inhibitors
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
2012
Comparative 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
Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans
Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans. Hypertension 2010, 56: 728-733. PMID: 20679179, PMCID: PMC3305047, DOI: 10.1161/hypertensionaha.110.156554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4Dose-Response Relationship, DrugDouble-Blind MethodDrug InteractionsDrug Therapy, CombinationEnalaprilFemaleHeart RateHemodynamicsHumansInsulinMaleMetabolic SyndromeMiddle AgedPeptidyl-Dipeptidase AProspective StudiesPyrazinesRenal CirculationSitagliptin PhosphateSodiumTriazolesConceptsDipeptidyl peptidase IV inhibitionACE inhibitionHypotensive responseHemodynamic effectsBlood pressureHeart rateSerum dipeptidyl peptidase IV activityAngiotensin-Converting Enzyme InhibitionAcute ACE inhibitionVasoconstrictor neuropeptide YBlood pressure responseRenal blood flowSympathetic nervous systemType 2 diabeticsCross-over fashionDipeptidyl peptidase IV inhibitorsDose-dependent effectDipeptidyl peptidase IV activityDose-dependent mannerPeptidase IV inhibitorsPeptidase IV activityMetabolic syndromeNorepinephrine concentrationsIncretin hormonesNeuropeptide Y
2009
Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome
Hill KD, Eckhauser AW, Marney A, Brown NJ. Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome. Diabetes Care 2009, 32: 857-859. PMID: 19196886, PMCID: PMC2671107, DOI: 10.2337/dc08-1862.Peer-Reviewed Original ResearchConceptsBeta-cell functionPhosphodiesterase-5 inhibitionMetabolic syndromeInsulin sensitivityPlasma renin activityDiastolic blood pressureΒ-cell functionRenin activityBlood pressureACE inhibitionAngiotensin IIFibrinolytic parametersACE activityGlucose homeostasisSeparate daysSyndromeRamiprilFibrinolysisTadalafilInhibitionTreatmentNovel strategyPlaceboResearch designWomen
2007
Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor–induced peritracheal edema
Byrd JB, Shreevatsa A, Putlur P, Foretia D, McAlexander L, Sinha T, Does MD, Brown NJ. Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor–induced peritracheal edema. Journal Of Allergy And Clinical Immunology 2007, 120: 403-408. PMID: 17531305, DOI: 10.1016/j.jaci.2007.04.012.Peer-Reviewed Original ResearchConceptsACE inhibitor-associated angioedemaDPPIV-deficient ratsMagnetic resonance imagingEdema formationSubstance PSerum dipeptidyl peptidase IV activityResonance imagingCaptopril-treated ratsSaline-treated ratsReceptor-dependent mechanismDipeptidyl peptidase IV activityPeptidase IV activityACE inhibitionSerial T2F344 ratsAnimal modelsEdemaAngioedemaDPPIV activityRatsDipeptidyl peptidase activityImpaired degradationSpantideDeficiencyMagnetic resonance
2003
Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass
Pretorius M, Murphey LJ, McFarlane JA, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass. Circulation 2003, 108: 3079-3083. PMID: 14656921, DOI: 10.1161/01.cir.0000105765.54573.60.Peer-Reviewed Original ResearchConceptsPostoperative day 1PAI-1 antigenCardiopulmonary bypassACE inhibitorsPAI-1 expressionACEI groupACE inhibitionPlasminogen activator inhibitor-1 (PAI-1) concentrationsTPA activityTissue-type plasminogen activator antigenAngiotensin-converting enzyme inhibitionAcute graft thrombosisPreoperative ACE inhibitorsMorning of surgeryCoronary artery bypassVein graft occlusionPlasminogen activator antigenArterial blood samplesArtery bypassGraft thrombosisGraft occlusionFibrinolytic responseAngiotensin IIBlood samplesDay 1Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin
Pretorius M, Rosenbaum D, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin. Circulation 2003, 107: 579-585. PMID: 12566370, DOI: 10.1161/01.cir.0000046268.59922.a4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood Flow VelocityBradykininBradykinin Receptor AntagonistsDose-Response Relationship, DrugEnalaprilatEndothelium, VascularFemaleFibrinolysisForearmHumansInfusions, Intra-ArterialMaleMethacholine ChlorideMuscarinic AgonistsRegional Blood FlowSmokingTissue Plasminogen ActivatorVascular ResistanceConceptsForearm blood flowNet t-PA releaseT-PA releaseEndothelial t-PA releaseHoe 140T-PA responseEndogenous bradykininACE inhibitionExogenous bradykininTissue-type plasminogen activator releaseReceptor antagonist HOE 140Angiotensin-Converting Enzyme InhibitionBradykinin receptor antagonist HOE 140Effects of enalaprilatIntra-arterial enalaprilatIntra-arterial infusionPlasminogen activator releaseEnzyme inhibitionFBF responseVascular resistanceBlood flowActivator releaseEnalaprilatBradykininMethacholine
2002
ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism
Brown NJ, Kumar S, Painter CA, Vaughan DE. ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism. Hypertension 2002, 40: 859-865. PMID: 12468570, DOI: 10.1161/01.hyp.0000040264.15961.48.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood GlucoseBlood PressureDiureticsDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansHydrochlorothiazideHypertensionInsulinInsulin ResistanceLosartanMaleMiddle AgedPlasminogen Activator Inhibitor 1RamiprilReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSodium Chloride Symporter InhibitorsTissue Plasminogen ActivatorTreatment OutcomeConceptsPlasminogen activator inhibitor-1PAI-1 antigenAngiotensin type 1 receptor antagonismPlasma PAI-1 antigenAT1 receptor antagonismReceptor antagonismACE inhibitionAddition of ramiprilAngiotensin receptor antagonismWeeks of hydrochlorothiazideEffects of losartanPlasma PAI-1Activator inhibitor-1Aldosterone systemHypertensive subjectsBlood pressureFibrinolytic variablesMyocardial infarctionTPA antigenRisk factorsTreatment periodLosartanTPA activityAntigenInhibitor-1Dipeptidyl Peptidase IV Activity in Patients With ACE-Inhibitor-Associated Angioedema
Lefebvre J, Murphey LJ, Hartert TV, Jiao Shan R, Simmons WH, Brown NJ. Dipeptidyl Peptidase IV Activity in Patients With ACE-Inhibitor-Associated Angioedema. Hypertension 2002, 39: 460-464. PMID: 11882590, DOI: 10.1161/hy0202.103054.Peer-Reviewed Original ResearchConceptsDPPIV activityHypertensive volunteersHypertensive subjectsRemote historyAcute ACE inhibitionSerum DPPIV activityUntreated hypertensive controlsUntreated hypertensive subjectsMetabolism of bradykininDipeptidyl peptidase IV activityAcute ACEIChronic ACEiPeptidase IV activityCorticosteroid treatmentHypertensive controlsHypertensive patientsNormotensive volunteersNormotensive controlsACE inhibitorsACE inhibitionSubstance PBradykinin degradationAssociated angioedemaACEIAngioedemaComparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women
Brown NJ, Abbas A, Byrne D, Schoenhard JA, Vaughan DE. Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women. Circulation 2002, 105: 304-309. PMID: 11804984, DOI: 10.1161/hc0302.102570.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBlood PressureCardiovascular DiseasesCross-Over StudiesDrug Therapy, CombinationEstradiolEstrogen Replacement TherapyEstrogens, Conjugated (USP)FemaleHumansMiddle AgedPlasminogen Activator Inhibitor 1Polymorphism, GeneticPostmenopauseRamiprilReninSingle-Blind MethodTissue Plasminogen ActivatorConceptsHealthy postmenopausal womenPAI-1 4G/5G genotypePlasma renin activityPostmenopausal womenPAI-1 concentrationsACE inhibitionTissue plasminogen activatorConjugated estrogensPAI-1G genotypeRenin activityAngiotensin IIPlasminogen activator inhibitor-1 (PAI-1) concentrationsAngiotensin-Converting Enzyme InhibitionPAI-1 antigen concentrationsPlasminogen activatorConjugated equine estrogensEffects of estrogenPlasminogen activator inhibitor-1Activator inhibitor-1Combination estrogenClinical outcomesEquine estrogensCombined therapyCrossover treatment
2001
Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm
Wilsdorf T, Gainer J, Murphey L, Vaughan D, Brown N. Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm. Hypertension 2001, 37: 1136-1140. PMID: 11304515, DOI: 10.1161/01.hyp.37.4.1136.Peer-Reviewed Original ResearchConceptsForearm blood flowAng IBlood flowTissue plasminogen activator responseTPA releaseAng I infusionDoses of AngHuman forearm vasculatureEffects of AngPeripheral vascular resistanceSystemic hemodynamic effectsRole of AngNormotensive subjectsVascular resistanceVasoconstrictor responsesVasodilator effectHemodynamic effectsBrachial arteryForearm vasculatureI infusionACE inhibitionSupraphysiological dosesRat modelConstant infusionAng
2000
Endogenous bradykinin and the renin and pressor responses to furosemide in humans.
Murphey LJ, Kumar S, Brown NJ. Endogenous bradykinin and the renin and pressor responses to furosemide in humans. Journal Of Pharmacology And Experimental Therapeutics 2000, 295: 644-8. PMID: 11046100.Peer-Reviewed Original ResearchConceptsPlasma renin activityMean arterial pressureHoe 140Renin responseEndogenous bradykininRenin activityArterial pressureHeart rateBasal plasma renin activityRenin-angiotensin systemAngiotensin I/Blood pressure regulationCrossover design studyAcute furosemide treatmentRenin regulationSpecific bradykininDiuretic responseFurosemide administrationFurosemide treatmentACE inhibitionReceptor antagonistPressure regulationBradykininFurosemideHumansInhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans.
Kim KS, Kumar S, Simmons WH, Brown NJ. Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans. Journal Of Pharmacology And Experimental Therapeutics 2000, 292: 295-8. PMID: 10604961.Peer-Reviewed Original ResearchConceptsDegradation of bradykininACE inhibitionWheal responseACE inhibitor quinaprilEffect of quinaprilNon-ACE pathwaysMetabolism of bradykininDose-response curveCardioprotective effectsIntradermal administrationIntradermal injectionOral administrationHealthy subjectsEnzyme inhibitorsSignificant interactionQuinaprilBradykininAminopeptidase PAngiotensinInhibitionAdministrationHuman skinPresent studyApstatinResponse
1998
Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1
Brown N, Agirbasli M, Williams G, Litchfield W, Vaughan D. Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1. Hypertension 1998, 32: 965-971. PMID: 9856958, DOI: 10.1161/01.hyp.32.6.965.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsCatecholaminesCircadian RhythmCreatinineDiet, Sodium-RestrictedFibrinolysisHemodynamicsHumansHydrocortisoneIsoquinolinesMalePlasminogen Activator Inhibitor 1QuinaprilReninRenin-Angiotensin SystemSodiumSupine PositionTetrahydroisoquinolinesTissue Plasminogen ActivatorConceptsLow salt intakeRenin-angiotensin systemPAI-1 antigenPlasma renin activitySalt intakeACE inhibitionMyocardial infarctionTPA antigenFibrinolytic systemPAI-1Plasminogen activator inhibitor-1 activityTissue-type plasminogen activator antigenPAI-1 antigen concentrationsPAI-1 antigen levelsThrombotic cardiovascular eventsHigh salt intakeLeft ventricular dysfunctionRecurrent myocardial infarctionPlasminogen activator antigenInhibitor-1 activityPlasma PAI-1PAI-1 activityConcomitant ACE inhibitionCardiovascular eventsRenin activityEffect of Bradykinin-Receptor Blockade on the Response to Angiotensin-Converting–Enzyme Inhibitor in Normotensive and Hypertensive Subjects
Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of Bradykinin-Receptor Blockade on the Response to Angiotensin-Converting–Enzyme Inhibitor in Normotensive and Hypertensive Subjects. New England Journal Of Medicine 1998, 339: 1285-1292. PMID: 9791144, DOI: 10.1056/nejm199810293391804.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood PressureBradykininBradykinin Receptor AntagonistsCaptoprilDiet, Sodium-RestrictedDrug InteractionsDrug Therapy, CombinationFemaleHumansHypertensionKidneyLosartanMaleReference ValuesRenin-Angiotensin SystemSingle-Blind MethodConceptsPlasma renin activityBlood pressureACE inhibitionHypertensive subjectsShort-term effectsRenin activitySpecific bradykinin receptor antagonistAngiotensin converting enzyme (ACE) inhibitorsAdministration of captoprilAdministration of losartanBradykinin receptor blockadeCoadministration of icatibantContribution of bradykininRenal hemodynamic responseNormal blood pressureRenin-angiotensin systemSeparate study daysBradykinin receptor antagonistDegradation of bradykininAntagonist losartanHypertensive personsHypotensive effectAngiotensin IIAngiotensin-ConvertingHemodynamic response
1996
Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin.
Brown NJ, Ryder D, Gainer JV, Morrow JD, Nadeau J. Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin. Journal Of Pharmacology And Experimental Therapeutics 1996, 279: 703-12. PMID: 8930174.Peer-Reviewed Original ResearchConceptsACE inhibitorsVasodepressor responseProstacyclin responsesEnzyme inhibitorsHigh-renin hypertensive patientsContribution of prostacyclinPlacebo-treated subjectsMean arterial pressureProstaglandin-independent mechanismEffect of bradykininDegradation of bradykininBradykinin doseProstacyclin metaboliteHypertensive patientsHypotensive responseVasodepressor effectArterial pressureBlood pressureACE inhibitionPGF1 alphaUrinary excretionProstacyclin productionProstaglandin productionBradykininClass effect