2017
Two Pools of Epoxyeicosatrienoic Acids in Humans
Elijovich F, Milne GL, Brown NJ, Laniado-Schwartzman M, Laffer CL. Two Pools of Epoxyeicosatrienoic Acids in Humans. Hypertension 2017, 71: 346-355. PMID: 29279315, PMCID: PMC5764817, DOI: 10.1161/hypertensionaha.117.10392.Peer-Reviewed Original ResearchConceptsSalt-resistant subjectsDihydroxyeicosatrienoic acidsEpoxyeicosatrienoic acidsBlood pressurePlasma epoxyeicosatrienoic acidsRegulation of natriuresisSalt-sensitive subjectsUrine sodium excretionPotential therapeutic implicationsRenal poolSodium excretionInpatient protocolNormotensive subjectsFractional excretionVascular dysfunctionVascular toneSystemic originTherapeutic implicationsTotal poolNatriuresisSalt loadingExcretionUrine poolsAldosteroneCatecholamines
2016
B-Type Natriuretic Peptide, Aldosterone, and Fluid Management in ARDS
Semler MW, Marney AM, Rice TW, Nian H, Yu C, Wheeler AP, Brown NJ, Network N. B-Type Natriuretic Peptide, Aldosterone, and Fluid Management in ARDS. CHEST Journal 2016, 150: 102-111. PMID: 27018313, PMCID: PMC4980545, DOI: 10.1016/j.chest.2016.03.017.Peer-Reviewed Original ResearchConceptsB-type natriuretic peptideAcute respiratory distress syndromeConservative fluid managementRespiratory distress syndromeLiberal fluid managementVentilator-free daysNatriuretic peptideFluid managementDistress syndromeAldosterone concentrationOverall mortalityB-type natriuretic peptide concentrationsCatheter Treatment TrialNatriuretic peptide concentrationsLow aldosterone concentrationsHospital mortalityMedian aldosteroneMultivariable analysisStudy enrollmentTreatment trialsPlasma concentrationsRetrospective analysisFluid balanceAldosteroneFluid strategy
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
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
2010
Aldosterone and inflammation
Gilbert KC, Brown NJ. Aldosterone and inflammation. Current Opinion In Endocrinology Diabetes And Obesity 2010, 17: 199-204. PMID: 20422780, PMCID: PMC4079531, DOI: 10.1097/med.0b013e3283391989.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptorAngiotensin subtype 1 receptorAldosterone-induced inflammationMineralocorticoid receptor activationVascular collagen depositionMineralocorticoid receptor antagonistsSubtype 1 receptorInflammatory cell infiltrationVascular smooth muscle cellsAldosterone synthase inhibitorsNuclear factor-kappaBSmooth muscle cellsCell-specific effectsInflammatory phenotypeReceptor antagonistTissue inflammationCell infiltrationTherapeutic roleCollagen depositionSynthase inhibitorAldosteroneFactor-kappaBInflammationReceptor activationMuscle cells
2008
Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta
Luther JM, Wang Z, Ma J, Makhanova N, Kim HS, Brown NJ. Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta. Endocrinology 2008, 150: 2229-2236. PMID: 19106220, PMCID: PMC2671907, DOI: 10.1210/en.2008-1296.Peer-Reviewed Original ResearchConceptsPpET-1 expressionAng IIPlasminogen activator inhibitor-1Profibrotic gene expressionEndogenous aldosteroneActivator inhibitor-1PAI-1MRNA expressionWT miceAngiotensin IITGF-beta mRNA expressionInhibitor-1Acute angiotensin IIBasal PAI-1Plasma renin activityAcute stimulatory effectPpET-1 mRNA expressionTGF-beta expressionTissue mRNA expressionPreproendothelin-1 expressionRenin activityAldosterone concentrationH infusionAldosteronePpET-1
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 evidenceAldosteronePatients
2006
Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor–Dependent Mechanism
Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, Brown NJ. Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor–Dependent Mechanism. Hypertension 2006, 48: 1050-1057. PMID: 17043157, DOI: 10.1161/01.hyp.0000248135.97380.76.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptor-dependent mechanismAngiotensin IIReceptor-dependent mechanismBlood pressureIL-6Normotensive subjectsCrossover studyHigh-sensitivity C-reactive proteinSerum IL-6 concentrationDouble-blind crossover studyOxidative stressWeeks of placeboIL-6 concentrationsC-reactive proteinRenal plasma flowIntravenous aldosteroneAldosterone responseSerum potassiumInterleukin-6Mineralocorticoid receptorPlaceboAldosteroneSpironolactoneSeparate daysReceptor independent
2005
Regression of Existing Glomerulosclerosis by Inhibition of Aldosterone
Aldigier JC, Kanjanbuch T, Ma LJ, Brown NJ, Fogo AB. Regression of Existing Glomerulosclerosis by Inhibition of Aldosterone. Journal Of The American Society Of Nephrology 2005, 16: 3306-3314. PMID: 16192423, DOI: 10.1681/asn.2004090804.Peer-Reviewed Original ResearchConceptsInhibition of aldosteroneAngiotensin type 1 receptor antagonistType 1 receptor antagonistAdult male Sprague-DawleySeverity of glomerulosclerosisDevelopment of glomerulosclerosisMale Sprague-DawleyEffect of inhibitionCONT ratsGlomerulosclerosis indexSerum creatinineSystolic BPAntihypertensive drugsReceptor antagonistSprague-DawleySP ratsGlomerulosclerosisSpironolactoneSame ratsRatsSP groupAldosteroneFurther treatmentWkInhibition
2003
Eplerenone
Brown NJ. Eplerenone. Circulation 2003, 107: 2512-2518. PMID: 12756192, DOI: 10.1161/01.cir.0000071081.35693.9a.Peer-Reviewed Original ResearchConceptsAldosterone receptor antagonistsReceptor antagonistMineralocorticoid receptor-dependent mechanismSelective aldosterone receptor antagonistAldosterone receptor antagonismRole of aldosteroneCongestive heart failureTreatment of hypertensionReceptor-dependent mechanismAntiandrogenic side effectsRenal injuryHeart failureReceptor antagonismCardiovascular toxicityClinical trialsSide effectsAnimal studiesEplerenoneAldosteroneAntagonistHypertensionPatientsSpironolactoneInjuryMortality
2002
Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans
Sawathiparnich P, Kumar S, Vaughan DE, Brown NJ. Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans. The Journal Of Clinical Endocrinology & Metabolism 2002, 87: 448-452. PMID: 11836266, DOI: 10.1210/jcem.87.2.7980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAldosteroneAntihypertensive AgentsBlood PressureCross-Over StudiesDiureticsDouble-Blind MethodFibrinolysisHumansHydrochlorothiazideHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1Sodium Chloride Symporter InhibitorsSpironolactoneConceptsPAI-1 antigenT-PA antigenAngiotensin IITissue-type plasminogen activator antigenEffect of spironolactoneSystolic blood pressureMale hypertensive subjectsPlasminogen activator antigenPlasminogen activator inhibitor-1Plasminogen activator inhibitor-1 productionActivator inhibitor-1PAI-1 productionAldosterone systemHypertensive subjectsSerum aldosteroneBlood pressureEndogenous aldosteroneHemodynamic parametersAldosteroneStudy daysSpironolactoneHCTZPAI-1AntigenInhibitor-1Aldosterone 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
2000
Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo
Brown N, Nakamura S, Ma L, Nakamura I, Donnert E, Freeman M, Vaughan D, Fogo A. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney International 2000, 58: 1219-1227. PMID: 10972684, DOI: 10.1046/j.1523-1755.2000.00277.x.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAnimalsBlood PressureBlotting, NorthernCreatinineDisease ProgressionFibrosisGene ExpressionGlomerulosclerosis, Focal SegmentalIn Situ HybridizationKidney GlomerulusMaleMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1ProteinuriaRatsRats, Sprague-DawleyRNA, MessengerSpironolactoneConceptsPlasminogen activator inhibitor-1PAI-1 expressionBlood pressurePAI-1 mRNA expressionActivator inhibitor-1Development of sclerosisAldosterone antagonismMRNA expressionMale Sprague-Dawley ratsInhibitor-1Aldosterone antagonist spironolactoneDegree of sclerosisSprague-Dawley ratsMajor physiological inhibitorAldosterone systemAntagonist spironolactoneRenal injuryFibrinolytic balanceSignificant proteinuriaCombination therapySingle doseRadiation injuryRat modelAT1RAAldosterone