2021
Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids
Luther JM, Wei DS, Ghoshal K, Peng D, Adler GK, Turcu AF, Nian H, Yu C, Solorzano CC, Pozzi A, Brown NJ. Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids. Hypertension 2021, 77: 1323-1331. PMID: 33583202, PMCID: PMC8320355, DOI: 10.1161/hypertensionaha.120.14808.Peer-Reviewed Original Research
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
2013
Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis
Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nature Reviews Nephrology 2013, 9: 459-469. PMID: 23774812, PMCID: PMC3922409, DOI: 10.1038/nrneph.2013.110.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAnimalsAromatase InhibitorsCardiovascular SystemCytochrome P-450 CYP11B2Endothelial CellsFadrozoleFibrosisHumansImidazolesInflammationKidneyMacrophagesMineralocorticoid Receptor AntagonistsMyocardiumMyocytes, CardiacPyridinesReactive Oxygen SpeciesReceptors, MineralocorticoidSodium, Dietary
2012
Lysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension
Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Chen Y, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension. American Journal Of Hypertension 2012, 25: 812-817. PMID: 22534796, PMCID: PMC3721725, DOI: 10.1038/ajh.2012.43.Peer-Reviewed Original ResearchConceptsMinor allele carriersSalt-sensitive hypertensionBlood pressureSingle nuclear polymorphismsAllele carriersHypertensive cohortDietary saltWT miceLiberal salt dietLiberal salt intakeSystolic blood pressureSerum aldosterone concentrationHeterozygote knockout miceTranslational research studiesRenovascular responsivenessAldosterone concentrationSalt dietDietary sodiumSalt intakeSystolic BPHuman studiesHypertensionKnockout miceClinical relevanceCaucasian cohort
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
2007
Aldosterone and end-organ damage
Marney AM, Brown NJ. Aldosterone and end-organ damage. Clinical Science 2007, 113: 267-278. PMID: 17683282, DOI: 10.1042/cs20070123.Peer-Reviewed Original ResearchConceptsMR antagonismBlood pressureEndothelial functionMyocardial infarctionGlucose homeostasisRapid non-genomic effectsEnd-organ damageImpairs endothelial functionNon-genomic effectsNon-genomic pathwaysResistant hypertensionAldosterone concentrationEndothelial dysfunctionRenal injuryDiabetic patientsMetabolic syndromeSleep apnoeaSubsequent fibrosisMR activationSodium retentionCardiac fibrosisCardiovascular remodellingBody of evidenceAldosteronePatientsModulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency
Brown NJ, Bradford J, Wang Z, Lea W, Ma L, Ma J, Vaughan DE, Fogo AB. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney International 2007, 72: 72-81. PMID: 17429342, DOI: 10.1038/sj.ki.5002268.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsAortaBlood PressureGene Expression RegulationKidneyLiverLosartanMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNorepinephrinePlasminogen Activator Inhibitor 1Random AllocationReceptor, Angiotensin, Type 1RNA, MessengerVasoconstrictor AgentsConceptsPAI-1 expressionPlasminogen activator inhibitor-1 expressionSystolic blood pressureAng IIBlood pressureReceptor deficiencyWT miceAngiotensin IIBaseline systolic blood pressureAT1a receptor deficiencyEffects of losartanReceptor knockout micePressor responseWT heartsReceptor mRNAKnockout miceLosartanNorepinephrinePAI-1AortaKidneyLiverMiceCell-type specificHeart
2004
Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension
Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O’Donnell C, Brown NJ, Waterman MR, Capdevila JH. Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension. Circulation 2004, 111: 63-69. PMID: 15611369, DOI: 10.1161/01.cir.0000151309.82473.59.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAllelesAmino Acid SubstitutionArachidonic AcidBlack PeopleBlood PressureCodonCohort StudiesComorbidityCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemDNA Mutational AnalysisFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic VariationGenotypeHumansHydroxyeicosatetraenoic AcidsHypertensionIntronsKidneyLauric AcidsMaleMiddle AgedMultifactorial InheritanceMutagenesis, InsertionalMutation, MissensePoint MutationSequence DeletionTennesseeUnited StatesWhite PeopleConceptsArachidonic acidORs of hypertensionBlood pressure controlBody mass indexEndogenous arachidonic acidLarge population databaseFramingham Heart StudySevere hypertensionEssential hypertensionHypertension comorbidityTubular functionHypertensive statusMass indexFunctional variantsHypertensionHeart StudyPressure controlCYP4A11Polygenic determinantsPopulation databaseTargeted disruptionHuman CYP4A11Acid synthaseAssociationSynthase activityPharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling
Weisberg AD, Albornoz F, Griffin JP, Crandall DL, Elokdah H, Fogo AB, Vaughan DE, Brown NJ. Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2004, 25: 365-371. PMID: 15576638, DOI: 10.1161/01.atv.0000152356.85791.52.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAdministration, OralAngiotensin IIAnimalsAntigens, DifferentiationAortaAortic DiseasesBlood PressureChemokine CCL2Collagen Type ICollagen Type IIIDrug Evaluation, PreclinicalFibronectinsFibrosisGene Expression RegulationGlomerulosclerosis, Focal SegmentalHeartHypertrophy, Left VentricularIndoleacetic AcidsIndolesKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1Random AllocationRNA, MessengerSialoglycoproteinsSingle-Blind MethodSodium Chloride, DietaryConceptsAng IIAortic remodelingCardiac fibrosisPAI-039PAI-1 inhibitionVascular remodelingCardiac hypertrophyMouse modelHeart/body weight ratioAng II/saltWall thickeningPharmacological inhibitionSmall molecule PAI-1 inhibitorAortic mRNA expressionHigh salt intakeAortic wall thickeningMale C57BL/6J miceBody weight ratioChemoattractant protein-1PAI-1 deficiencyPAI-1 activityPAI-1 inhibitorPlasminogen activator inhibitorPressor responseAngiotensin IIUric acid and the state of the intrarenal renin-angiotensin system in humans
Perlstein TS, Gumieniak O, Hopkins PN, Murphey LJ, Brown NJ, Williams GH, Hollenberg NK, Fisher ND. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney International 2004, 66: 1465-1470. PMID: 15458439, DOI: 10.1111/j.1523-1755.2004.00909.x.Peer-Reviewed Original ResearchConceptsIntrarenal renin-angiotensin systemRenin-angiotensin systemSerum uric acid concentrationBody mass indexHigh-density lipoproteinUric acid concentrationRenal vascular responsePlasma renin activityAng IIRPF responseExperimental hyperuricemiaBlood pressureVascular responsesUric acidRenal plasma flow responsePara-aminohippuric acid clearanceHigh sodium balanceIntrarenal RAS activityRenal vascular responsivenessExogenous angiotensin IISerum high-density lipoproteinSerum uric acidMultivariable regression analysisPlasma flow responseRenin activity
2003
Characterization of the CYP4A11 gene, a second CYP4A gene in humans
Bellamine A, Wang Y, Waterman MR, Gainer JV, Dawson EP, Brown NJ, Capdevila JH. Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Archives Of Biochemistry And Biophysics 2003, 409: 221-227. PMID: 12464262, DOI: 10.1016/s0003-9861(02)00545-3.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBlotting, SouthernCloning, MolecularCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemExonsGene DeletionHumansHydroxyeicosatetraenoic AcidsIntronsKidneyMixed Function OxygenasesModels, GeneticMolecular Sequence DataPolymerase Chain ReactionProtein IsoformsReverse Transcriptase Polymerase Chain ReactionRNA
2002
Aldosterone and PAI-1: implications for renal injury.
Brown NJ, Vaughan DE, Fogo AB. Aldosterone and PAI-1: implications for renal injury. Journal Of Nephrology 2002, 15: 230-5. PMID: 12113592.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Activator inhibitor-1Renal injuryAnimal modelsInhibitor-1Aldosterone receptor antagonismPlasminogen activator inhibitor-1 expressionExtracellular matrix accumulationPAI-1 expressionMajor physiological inhibitorRenal diseaseAngiotensin IIReceptor antagonismClinical managementAldosteroneProduction of plasminPAI-1FibrosisMatrix accumulationPlasminogen activatorInjuryPhysiological inhibitorVivoExpressionDisease
1998
Effect 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
Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans.
Gandhi S, Ryder D, Brown N. Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans. Hypertension 1996, 28: 961-6. PMID: 8952583, DOI: 10.1161/01.hyp.28.6.961.Peer-Reviewed Original ResearchConceptsRenal plasma flow responseExogenous Ang IIRenal plasma flowBaseline renal plasma flowPara-aminohippurate clearanceAng IIAldosterone levelsPlasma flow responseAngiotensin IIAng II type 1 receptor blockadeAng II type 1 receptorFlow responseBaseline plasma aldosterone levelsType 1 receptor blockadeII type 1 receptorAng II doseBaseline systolic pressureRenal vascular responseAng II infusionEffects of losartanPlasma aldosterone levelsSystolic pressure responseType 1 receptorAbsence of losartanPmol/L