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
2014
Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans
Laffer CL, Elijovich F, Eckert GJ, Tu W, Pratt JH, Brown NJ. Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans. International Journal Of Cardiology Cardiovascular Risk And Prevention 2014, 8: 475-480. PMID: 25064769, PMCID: PMC4115247, DOI: 10.1016/j.jash.2014.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBlack or African AmericanBlood PressureCytochrome P-450 CYP4ACytochrome P-450 Enzyme SystemDNADouble-Blind MethodFemaleGenetic VariationGenotypeHumansHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPilot ProjectsRadioimmunoassayUnited StatesYoung AdultConceptsBlood pressure responseBlood pressureReceptor antagonismPressure responseMineralocorticoid receptor antagonismSalt-sensitive hypertensionAfrican AmericansExploratory pilot studyGC individualsAldosterone responseResistant hypertensionAntihypertensive effectTreatment responsePrecluded analysisCC genotypeCC homozygotesSpironolactoneC alleleHypertensionPilot studyENaC activationCYP4A11AmilorideActivation of ENaC.ENaC inhibition
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
Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury
Luther JM, Luo P, Wang Z, Cohen SE, Kim HS, Fogo AB, Brown NJ. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury. Kidney International 2012, 82: 643-651. PMID: 22622494, PMCID: PMC3434275, DOI: 10.1038/ki.2012.170.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAnimalsAortaBiomarkersBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalFibrosisGene Expression RegulationHeart DiseasesInflammationKidney DiseasesKidney GlomerulusMiceMice, 129 StrainMice, Inbred C57BLMineralocorticoid Receptor AntagonistsMyocardiumReceptors, MineralocorticoidRenin-Angiotensin SystemSodium Chloride, DietarySpironolactoneTime FactorsVascular DiseasesConceptsMineralocorticoid receptor antagonismAbsence of aldosteroneAldosterone deficiencyAngiotensin IIReceptor antagonismMineralocorticoid receptorKnockout miceAldosterone synthase knockout (AS(-/-)) miceMineralocorticoid receptor antagonist spironolactonePlasminogen activator inhibitor-1 mRNA expressionAldosterone synthase inhibitionMineralocorticoid receptor activationPrevents angiotensin IIAngiotensin II treatmentSynthase knockout miceBlood urea nitrogenWild-type miceWild-type littermatesMineralocorticoid antagonismAntagonist spironolactoneAortic remodelingRenal injuryEndogenous aldosteroneGlomerular hypertrophyGlomerular injury
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 ResearchMeSH KeywordsAldosteroneAnimalsCytochrome P-450 CYP11B2Disease Models, AnimalHumansInflammationMineralocorticoid Receptor AntagonistsReactive Oxygen SpeciesReceptor, Angiotensin, Type 1Receptors, MineralocorticoidConceptsMineralocorticoid 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
2009
Aldosterone 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 ResearchMeSH KeywordsAngiotensin IIAnimalsCytochrome P-450 CYP11B2Enzyme InhibitorsFibrosisHeart DiseasesKidney DiseasesMineralocorticoid Receptor AntagonistsRatsSodium Chloride, DietarySpironolactoneConceptsAldosterone 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
2008
Salt in the Wound
Brown NJ. Salt in the Wound. Journal Of The American Society Of Nephrology 2008, 20: 5-6. PMID: 19118146, DOI: 10.1681/asn.2008111185.Peer-Reviewed Original ResearchAldosteroneAnimalsKidney DiseasesKidney Tubules, CollectingMineralocorticoid Receptor AntagonistsNF-kappa BRatsReceptors, MineralocorticoidSclerosisSodium ChlorideSodium Chloride, Dietary
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 ResearchMeSH KeywordsAldosteroneCardiovascular DiseasesDiabetes MellitusEndothelium, VascularHumansKidneyKidney DiseasesMineralocorticoid Receptor AntagonistsMyocardiumReceptors, MineralocorticoidRenin-Angiotensin SystemConceptsMR 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
Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia
Ma J, Albornoz F, Yu C, Byrne DW, Vaughan DE, Brown NJ. Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia. Hypertension 2005, 46: 326-332. PMID: 15998706, DOI: 10.1161/01.hyp.0000174327.53863.86.Peer-Reviewed Original ResearchMeSH KeywordsAdultCross-Over StudiesDiureticsDouble-Blind MethodElectrolytesFemaleFibrinolysisHemodynamicsHumansHydrochlorothiazideHypertensionMaleMiddle AgedMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1PotassiumReceptors, MineralocorticoidRenin-Angiotensin SystemSodium Chloride Symporter InhibitorsSpironolactoneTriamtereneConceptsPAI-1 antigenMineralocorticoid receptor antagonismHypertensive subjectsPAI-1 responseTissue-type plasminogen activatorAldosterone systemNormotensive subjectsFibrinolytic balanceReceptor antagonismMelanocortin 4 receptor-deficient micePlasminogen activator inhibitor-1 (PAI-1) concentrationsEffect of spironolactoneReceptor-deficient miceEffect of triamtereneBlood pressureSerum potassiumTreatment groupsEffects of activationSpironolactonePAI-1Plasminogen activatorAntigenTriamtereneRegression analysisSubjectsAldosterone and end-organ damage
Brown NJ. Aldosterone and end-organ damage. Current Opinion In Nephrology & Hypertension 2005, 14: 235-241. PMID: 15821416, DOI: 10.1097/01.mnh.0000165889.60254.98.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneCardiovascular DiseasesFibrosisHumansKidney DiseasesMineralocorticoid Receptor AntagonistsModels, AnimalNitric OxideOxidative StressReceptors, MineralocorticoidConceptsMineralocorticoid receptor antagonismCongestive heart failureHeart failureReceptor antagonismMineralocorticoid receptorOxidative stressMineralocorticoid receptor-dependent mechanismEndothelial nitric oxide synthaseContribution of aldosteroneEnd-organ damageReceptor-independent effectsMineralocorticoid receptor agonistRecent clinical studiesInduction of inflammationNitric oxide synthaseRapid nongenomic mechanismsReceptor-dependent mechanismExtracellular matrix turnoverMineralocorticoid antagonismInflammatory markersCardiovascular mortalityEndothelial dysfunctionRenal injuryEndothelial functionRenal disease
2003
Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1
Sawathiparnich P, Murphey LJ, Kumar S, Vaughan DE, Brown NJ. Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 3867-3873. PMID: 12915681, DOI: 10.1210/jc.2003-030374.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsBenzimidazolesBiphenyl CompoundsDiureticsElectrolytesFemaleFibrinolysisFurosemideHemodynamicsHumansMaleMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1Potassium ChlorideReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSingle-Blind MethodSpironolactoneTetrazolesConceptsMean arterial pressureAldosterone receptor antagonismAng IIReceptor antagonismPAI-1Angiotensin II type 1Coadministration of spironolactoneEffects of candesartanFurosemide-induced increasePresence of candesartanAldosterone receptor antagonistsEndogenous Ang IIPlasminogen activator inhibitor-1PAI-1 antigenActivator inhibitor-1PAI-1 productionPlasminogen activator inhibitorAldosterone systemNormotensive subjectsArterial pressureAngiotensin IIAT1 receptorFibrinolytic variablesReceptor antagonistCandesartanEplerenone
Brown NJ. Eplerenone. Circulation 2003, 107: 2512-2518. PMID: 12756192, DOI: 10.1161/01.cir.0000071081.35693.9a.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAnimalsCardiovascular DiseasesCardiovascular SystemDisease Models, AnimalEplerenoneHumansHypertensionMineralocorticoid Receptor AntagonistsRenin-Angiotensin SystemSpironolactoneTreatment OutcomeConceptsAldosterone 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-1
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