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
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
2011
This is not Dr. Conn's aldosterone anymore.
Brown NJ. This is not Dr. Conn's aldosterone anymore. Transactions Of The American Clinical And Climatological Association 2011, 122: 229-43. PMID: 21686229, PMCID: PMC3116341.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsAnimalsBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalEnzyme InhibitorsFibrosisGene Expression RegulationHumansHyperaldosteronismInflammation MediatorsKidneyLigandsMiceMineralocorticoid Receptor AntagonistsMyocardiumRatsReceptors, MineralocorticoidSignal TransductionTime FactorsConceptsMR-independent pathwayPrevalence of hyperaldosteronismAngiotensin receptor blockersMineralocorticoid receptor antagonismSecretion of aldosteroneAldosterone-secreting adenomasPro-fibrotic effectsReceptor blockersResistant hypertensionSevere hypertensionAldosterone concentrationRenal injuryEndogenous aldosteroneACE inhibitorsCardiovascular remodelingAngiotensin IIReceptor antagonismHeart diseaseProfibrotic effectsAldosteroneBaseline valuesEnzyme inhibitorsPatientsPotassium homeostasisHypertension
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 responseAldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt
Lea WB, Kwak ES, Luther JM, Fowler SM, Wang Z, Ma J, Fogo AB, Brown NJ. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney International 2009, 75: 936-944. PMID: 19225557, PMCID: PMC2770712, DOI: 10.1038/ki.2009.9.Peer-Reviewed Original ResearchConceptsAldosterone synthase inhibitionEnd-organ damageHigh salt intakeWeeks of treatmentPlasminogen activator inhibitor-1Angiotensin IISynthase inhibitionMRNA expressionSalt intakeInterstitial fibrosisGrowth factor-beta mRNA expressionAortic medial hypertrophyMineralocorticoid receptor blockadeMineralocorticoid receptor antagonismHigh-salt dietCardiac interstitial fibrosisKidneys of ratsPAI-1 mRNA expressionActivator inhibitor-1MRNA protein expressionAldosterone antagonismHypertensive responseRenal effectsUninephrectomized ratsMedial hypertrophy
2006
Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition
Brown NJ, Muldowney JA, Vaughan DE. Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition. Hypertension 2006, 47: 441-448. PMID: 16432054, DOI: 10.1161/01.hyp.0000202478.79587.1a.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsArginineDouble-Blind MethodDrug CombinationsEnzyme InhibitorsFemaleFibrinolysisHemodynamicsHumansInfusions, IntravenousMaleMiddle AgedNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlasminogen Activator Inhibitor 1ProdrugsRamiprilReference ValuesRenin-Angiotensin SystemConceptsPlasminogen activator inhibitor-1Plasminogen activator inhibitor-1 antigenActivator inhibitor-1Salt-replete subjectsL-arginineFibrinolytic balanceInhibitor-1Angiotensin-Converting Enzyme InhibitionNO precursor L-argininePlasminogen activator inhibitor antigenTissue-type plasminogen activator antigenEffect of angiotensinPrecursor L-argininePlasminogen activator antigenNO synthase inhibitorEnzyme inhibitionT-PA activityRenin activityD-dimerInhibitor antigenNormal subjectsSynthase inhibitorEnzyme inhibitorsT-PAAntigen
2004
NO Synthase Inhibition Increases Aldosterone in Humans
Muldowney JA, Davis SN, Vaughan DE, Brown NJ. NO Synthase Inhibition Increases Aldosterone in Humans. Hypertension 2004, 44: 739-745. PMID: 15381675, DOI: 10.1161/01.hyp.0000143852.48258.f1.Peer-Reviewed Original ResearchConceptsL-NAME infusionL-NAMEL-arginineAldosterone concentrationSerum potassiumNitro-L-arginine methyl esterNO precursor L-arginineEndogenous NO modulatesDouble-blind treatmentPlasma renin activityAngiotensin II concentrationEnzyme inhibitor ramiprilSystolic blood pressurePrecursor L-arginineRenin activityPlacebo pretreatmentBlood pressureSerum aldosteroneTreatment armsNO modulatesVehicle infusionHeart rateNormal subjectsSeparate daysCombined treatment
2002
Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Schoenhard JA, Painter CA, Ripley RT, Brown NJ, Fogo AB, Vaughan DE. Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition. Journal Of Molecular And Cellular Cardiology 2002, 34: 617-627. PMID: 12054849, DOI: 10.1006/jmcc.2002.2001.Peer-Reviewed Original ResearchConceptsSystolic blood pressureNitric oxide synthase inhibitionOxide synthase inhibitionPerivascular fibrosisBlood pressurePAI-1 deficiencyCoronary perivascular fibrosisPlasminogen activator systemL-NAMENOS inhibitionSynthase inhibitionDeficient miceVascular pathologyLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterL-NAME-induced hypertensionLong-term NOS inhibitionPlasma TGF-beta1 levelsPlasminogen activator inhibitor-1-deficient miceStructural vascular changesTGF-beta1 levelsLong-term treatmentTissue-type plasminogen activator-deficient miceWeek study periodActivator system
2001
Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Fogo A, Ma L, Schoenhard J, Brown N, Vaughan D. Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition. Circulation 2001, 104: 839-844. PMID: 11502712, DOI: 10.1161/hc3301.092803.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureBody WeightCollagenCoronary VesselsEnzyme InhibitorsFibrosisHemodynamicsHypertensionHypertrophy, Left VentricularMaleMiceMice, Inbred C57BLMice, KnockoutNG-Nitroarginine Methyl EsterNitric Oxide SynthasePlasminogen Activator Inhibitor 1Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerTimeConceptsPlasminogen activator inhibitor-1Systolic blood pressureLong-term NOS inhibitionBlood pressurePAI-1 deficiencyNitric oxide synthaseCoronary perivascular fibrosisPerivascular fibrosisNOS inhibitionWT miceLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterNitric oxide synthase inhibitionWild-type male miceControl WT miceStructural vascular changesOxide synthase inhibitionArteriosclerotic cardiovascular diseaseDevelopment of fibrosisPAI-1 activityNew therapeutic strategiesActivator inhibitor-1Cardiac type ILong-term inhibitionPrevents hypertension