2017
Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery
Shuey MM, Billings FT, Wei S, Milne GL, Nian H, Yu C, Brown NJ. Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery. PLOS ONE 2017, 12: e0175292. PMID: 28552948, PMCID: PMC5446112, DOI: 10.1371/journal.pone.0175292.Peer-Reviewed Original ResearchConceptsAcute kidney injuryChronic kidney diseaseCardiac surgery cohortSoluble epoxide hydrolaseCardiac surgeryKidney injurySurgery cohortAcute Kidney Injury Network criteriaIncidence of AKIPostoperative acute kidney injuryPercent of patientsGlomerular filtration rateBody mass indexAssociation of gainsRenal injuryCardiopulmonary bypassWhite patientsMass indexKidney diseaseFiltration ratePharmacological strategiesDiscovery cohortNetwork criteriaVariant carriersSEH activity
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
Review: Therapeutic potential of plasminogen activator inhibitor-1 inhibitors
Brown NJ. Review: Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Therapeutic Advances In Cardiovascular Disease 2010, 4: 315-324. PMID: 20660535, DOI: 10.1177/1753944710379126.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Plasminogen Activator Inhibitor-1 InhibitorsInitiation of diabetesPathogenesis of thrombosisPotential therapeutic strategyActivator inhibitor-1Major physiological inhibitorRenal injuryVascular remodelingPreclinical studiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic potentialInhibitor-1Physiological inhibitorMolecule inhibitorsCell migrationInhibitorsThrombosisDiabetesFibrosisPathogenesisFibrinolysisInjuryDisease
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
2005
Aldosterone and end-organ damage
Brown N. Aldosterone and end-organ damage. Current Opinion In Internal Medicine 2005, 4: 381-387. DOI: 10.1097/00132980-200508000-00009.Peer-Reviewed Original ResearchMineralocorticoid 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 mechanismPurpose of reviewExtracellular matrix turnoverMineralocorticoid antagonismInflammatory markersCardiovascular mortalityEndothelial dysfunctionRenal injuryEndothelial functionAldosterone 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
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
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
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