2018
DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition
Hubers SA, Wilson JR, Yu C, Nian H, Grouzmann E, Eugster P, Shibao CA, Billings FT, Jafarian Kerman S, Brown NJ. DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition. Hypertension 2018, 72: 712-719. PMID: 29987109, PMCID: PMC6202157, DOI: 10.1161/hypertensionaha.118.11498.Peer-Reviewed Original ResearchConceptsNPY infusionPlacebo-controlled crossover studyAngiotensin-converting enzyme inhibitorAldosterone system inhibitionDose-dependent vasoconstrictionIntra-arterial enalaprilatAngiotensin receptor blockersForearm blood flowHigh-risk patientsOrder of treatmentReceptor blockersVasoconstrictor effectVasoconstrictor responsesCardiovascular effectsRenin-AngiotensinBrachial arteryHeart failureNorepinephrine releaseCrossover studyEndogenous NPYY1 receptorCrossover treatmentSystem inhibitionY2 receptorsDPP4 inhibition
2016
Combined 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
2009
Dipeptidyl Peptidase-IV Inhibitor Use Associated With Increased Risk of ACE Inhibitor-Associated Angioedema
Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA. Dipeptidyl Peptidase-IV Inhibitor Use Associated With Increased Risk of ACE Inhibitor-Associated Angioedema. Hypertension 2009, 54: 516-523. PMID: 19581505, PMCID: PMC2758288, DOI: 10.1161/hypertensionaha.109.134197.Peer-Reviewed Original ResearchConceptsACE inhibitorsRisk of angioedemaVildagliptin useDPP-IV inhibitorsComparator-treated patientsEnzyme (ACE) inhibitor-associated angioedemaStudy drug exposureAngiotensin receptor blockersPhase III studyPossible drug-drug interactionsIncidence of angioedemaCase report formsDipeptidyl peptidase IV inhibitorsDrug-drug interactionsDPP-IV inhibitor vildagliptinPathogenesis of angiotensinPeptidase IV inhibitorsAngioedema riskClinical angioedemaReceptor blockersIII studyAbsolute riskAdjudication committeeDPP-IV inhibitionDrug exposure
2008
Bradykinin 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
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
Inhibition 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
1991
Caffeine potentiates the renin response to diazoxide in man. Evidence for a regulatory role of endogenous adenosine.
Brown NJ, Porter J, Ryder D, Branch RA. Caffeine potentiates the renin response to diazoxide in man. Evidence for a regulatory role of endogenous adenosine. Journal Of Pharmacology And Experimental Therapeutics 1991, 256: 56-61. PMID: 1988669.Peer-Reviewed Original ResearchConceptsRenin responseEndogenous adenosineRenin releaseDiazoxide infusionAdenosine inhibitsRegulation of reninCross-over studyAdministration of diazoxideAdenosine receptor blockerModest tachycardiaPRA responseReceptor blockersBP responseLoading dosePRA measurementsContinuous infusionNormal subjectsStudy daysDiazoxideMaximal pulseInfusionPresence of caffeineReninCaffeineAdenosine