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
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
2014
Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans
Luther JM, Byrne LM, Yu C, Wang TJ, Brown NJ. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: e1895-e1902. PMID: 25029426, PMCID: PMC4184066, DOI: 10.1210/jc.2014-2122.Peer-Reviewed Original ResearchConceptsHigh sodium dietHigh sodium intakeInsulin sensitivity indexSodium intakeInsulin secretionAldosterone systemAldosterone infusionInsulin sensitivityAcademic clinical research centerAcute insulin secretory responseLow dietary sodium intakeDecrease insulin secretionC-peptide responsePlasma renin activityDietary sodium intakeLow sodium dietSystolic blood pressureClinical Research CenterInsulin secretory responseAcute insulin responseHigh-risk individualsImpairs insulin secretionGlucose-stimulated insulinIncident diabetesNormotensive volunteers
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
Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonismThis 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
Low-salt diet increases insulin resistance in healthy subjects
Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism 2010, 60: 965-968. PMID: 21036373, PMCID: PMC3036792, DOI: 10.1016/j.metabol.2010.09.005.Peer-Reviewed Original ResearchConceptsLow-salt dietHomeostasis model assessment indexModel assessment indexBody mass indexInsulin resistanceLS dietUrine aldosteroneMass indexHS dietHealthy subjectsHigher homeostasis model assessment indexUrine norepinephrine excretionPlasma renin activityHigh-salt dietSympathetic nervous systemSerum angiotensin IIPathogenesis of diabetesUrine epinephrineNorepinephrine excretionRenin activitySerum aldosteroneBlood pressureSerum sodiumAngiotensin IIHealthy menInteractive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans
Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans. Hypertension 2010, 56: 728-733. PMID: 20679179, PMCID: PMC3305047, DOI: 10.1161/hypertensionaha.110.156554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4Dose-Response Relationship, DrugDouble-Blind MethodDrug InteractionsDrug Therapy, CombinationEnalaprilFemaleHeart RateHemodynamicsHumansInsulinMaleMetabolic SyndromeMiddle AgedPeptidyl-Dipeptidase AProspective StudiesPyrazinesRenal CirculationSitagliptin PhosphateSodiumTriazolesConceptsDipeptidyl peptidase IV inhibitionACE inhibitionHypotensive responseHemodynamic effectsBlood pressureHeart rateSerum dipeptidyl peptidase IV activityAngiotensin-Converting Enzyme InhibitionAcute ACE inhibitionVasoconstrictor neuropeptide YBlood pressure responseRenal blood flowSympathetic nervous systemType 2 diabeticsCross-over fashionDipeptidyl peptidase IV inhibitorsDose-dependent effectDipeptidyl peptidase IV activityDose-dependent mannerPeptidase IV inhibitorsPeptidase IV activityMetabolic syndromeNorepinephrine concentrationsIncretin hormonesNeuropeptide YAldosterone 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
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 ResearchEndogenous 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-1Aldosterone and Vascular Inflammation
Brown NJ. Aldosterone and Vascular Inflammation. Hypertension 2008, 51: 161-167. PMID: 18172061, DOI: 10.1161/hypertensionaha.107.095489.Peer-Reviewed Original Research
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 independentPlasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury
Ma J, Weisberg A, Griffin JP, Vaughan DE, Fogo AB, Brown NJ. Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury. Kidney International 2006, 69: 1064-1072. PMID: 16528256, DOI: 10.1038/sj.ki.5000201.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAldosteroneAnimalsBlood PressureChemokine CCL2CollagenFibronectinsGene ExpressionGlomerulonephritisHemodynamicsKidney GlomerulusMacrophagesMaleMiceMice, Inbred C57BLMice, Inbred StrainsMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1RNA, MessengerSialoglycoproteinsSodiumConceptsMonocyte chemoattractant protein-1Plasminogen activator inhibitor-1WT miceGlomerular injuryPlasminogen activator inhibitor-1 deficiencyCollagen IIIMRNA expressionPAI-1-deficient miceRenal collagen contentRenal osteopontin expressionSodium/potassium ratioUrine albumin excretionSystolic blood pressureRenal mRNA expressionChemoattractant protein-1Activator inhibitor-1Collagen IGrowth factor betaAlbumin excretionSodium excretionBlood pressureMesangial expansionRenal expressionCardiac injuryUrine volumeEndogenous 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
2005
Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia
Williams JS, Williams GH, Raji A, Jeunemaitre X, Brown NJ, Hopkins PN, Conlin PR. Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. Journal Of Human Hypertension 2005, 20: 129-136. PMID: 16292348, DOI: 10.1038/sj.jhh.1001948.Peer-Reviewed Original ResearchConceptsHigh sodium dietPrimary hyperaldosteronismModerate hypertensionSodium restrictionHypertensive populationLow serum potassium levelsNormotensive control populationSerum potassium levelsHigh blood pressureSpecific cutoff valuesElevated AERElevated ARRHaemodynamic testingNormotensive populationResistant hypertensionHypertensive subjectsNormotensive subjectsSerum aldosteroneBlood pressureEssential hypertensivesMedication washoutStudy protocolHypokalaemiaCutoff valueControl populationAldosterone 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 ResearchConceptsMineralocorticoid 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