2020
Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data
Shuey M, Perkins B, Nian H, Yu C, Luther JM, Brown N. Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data. BMJ Open 2020, 10: e033100. PMID: 32461291, PMCID: PMC7259833, DOI: 10.1136/bmjopen-2019-033100.Peer-Reviewed Original ResearchConceptsBody mass indexHigher body mass indexElectronic medical recordsBaseline systolic BPTherapy-resistant hypertensionBlood pressure responseRetrospective cohort studyDiastolic BPSystolic BPBP responseBaseline BPCohort studyChronic kidney disease stage 3Real-world clinical settingElectronic medical record dataMean systolic BPDisease stage 3Glomerular filtration rateIschemic heart diseasePressure responseMedical record dataClinical trial dataHigh-density lipoproteinLow-density lipoproteinAcademic medical center
2012
Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery*
Pretorius M, Murray KT, Yu C, Byrne JG, Billings FT, Petracek MR, Greelish JP, Hoff SJ, Ball SK, Mishra V, Body SC, Brown NJ. Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery*. Critical Care Medicine 2012, 40: 2805-2812. PMID: 22824930, PMCID: PMC3588582, DOI: 10.1097/ccm.0b013e31825b8be2.Peer-Reviewed Original ResearchConceptsAcute renal failureAngiotensin-converting enzyme inhibitorMineralocorticoid receptor blockadePostoperative atrial fibrillationMineralocorticoid receptor antagonistsAtrial fibrillationPlacebo groupSpironolactone groupRenal failureCardiac surgeryReceptor blockadeReceptor antagonistEnzyme inhibitorsDouble-blind placebo-controlled studyAngiotensin-converting enzyme inhibitionPrevalence of hypotensionElective cardiac surgeryPlacebo-controlled studyRenin-angiotensin systemNormal sinus rhythmEnzyme inhibitionRamipril groupSpironolactone useHospital stayPrimary endpointObesity and Oxidative Stress Predict AKI after Cardiac Surgery
Billings FT, Pretorius M, Schildcrout JS, Mercaldo ND, Byrne JG, Ikizler TA, Brown NJ. Obesity and Oxidative Stress Predict AKI after Cardiac Surgery. Journal Of The American Society Of Nephrology 2012, 23: 1221-1228. PMID: 22626819, PMCID: PMC3380645, DOI: 10.1681/asn.2011090940.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAngiotensin-Converting Enzyme InhibitorsBiomarkersBody Mass IndexCardiac Surgical ProceduresDiureticsF2-IsoprostanesFemaleHumansInterleukin-6MaleMiddle AgedObesityOxidative StressPlasminogen Activator Inhibitor 1Postoperative ComplicationsRamiprilRandomized Controlled Trials as TopicRisk FactorsSignal TransductionSpironolactoneAldosterone 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
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
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 treatmentWkInhibitionMelanocortin-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 analysisSubjects
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 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-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