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
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
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 ResearchConceptsAldosterone 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 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
2005
The Kallikrein-Kinin System: Current and Future Pharmacological Targets
Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A. The Kallikrein-Kinin System: Current and Future Pharmacological Targets. Journal Of Pharmacological Sciences 2005, 99: 6-38. PMID: 16177542, DOI: 10.1254/jphs.srj05001x.Peer-Reviewed Original ResearchMeSH KeywordsAngioedemaAngiotensin-Converting Enzyme InhibitorsAnimalsAprotininBradykininBradykinin B2 Receptor AntagonistsCardiovascular DiseasesComplement C1 Inactivator ProteinsComplement C1 Inhibitor ProteinHumansInflammationKallikrein-Kinin SystemKallikreinsKidney DiseasesKininsNeprilysinPeptidyl-Dipeptidase APolymorphism, GeneticPyridinesRandomized Controlled Trials as TopicReceptor, Bradykinin B1Receptor, Bradykinin B2SerpinsThiazepinesConceptsKallikrein-kinin systemMultiple pharmacological interventionsPrecursors of kininsFuture pharmacological targetsProinflammatory effectsVasoactive kininsPharmacological interventionsCardiovascular propertiesPharmacological targetsComplement pathwayKininsActive kininsPathological processesPharmacological activitiesPlasma kallikreinMetabolic cascadeImportant metabolic pathwaysMetabolic pathwaysAntiproteasesAldosterone 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
2002
The Renin-Angiotensin-Aldosterone System and Fibrinolysis in Progressive Renal Disease
Brown NJ, Vaughan DE, Fogo AB. The Renin-Angiotensin-Aldosterone System and Fibrinolysis in Progressive Renal Disease. Seminars In Nephrology 2002, 22: 399-406. PMID: 12224047, DOI: 10.1053/snep.2002.34725.Peer-Reviewed Original ResearchMeSH KeywordsDisease ProgressionFibrinolysisHumansKidney DiseasesPlasminogen Activator Inhibitor 1Renin-Angiotensin SystemConceptsPlasminogen activator inhibitor-1Renal diseaseAldosterone systemProgressive renal diseaseFinal common pathwayActivator inhibitor-1Extracellular matrix accumulationPAI-1 expressionInitiating injuryRenal failureRenin-AngiotensinInterstitial fibrosisClinical managementMajor physiologic inhibitorAnimal modelsProduction of plasminFibrosisMatrix accumulationPlasminogen activatorPhysiologic inhibitorInhibitor-1Common pathwayDiseaseInjuryRAASAldosterone 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