2022
DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment
Wilson JR, Garner EM, Mashayekhi M, Hubers SA, Bustamante C, Kerman SJ, Nian H, Shibao CA, Brown NJ. DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment. Hypertension 2022, 79: 827-835. PMID: 35045722, PMCID: PMC8917054, DOI: 10.1161/hypertensionaha.121.18348.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensinsAprepitantBlood PressureCardiovascular AgentsCatecholaminesCross-Over StudiesDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4HumansNorepinephrineRamiprilRenin-Angiotensin SystemSitagliptin PhosphateValsartanConceptsDPP4 inhibitionBlood pressureACE inhibitionDouble-blind crossover studyAcute ACE inhibitionBlood pressure armNK1 receptor blockerACE inhibitor treatmentOral diabetes medicationsCalcium channel blockersType 2 diabetesEffects of DPP4Aldosterone systemCardiovascular complicationsDiabetes medicationsReceptor blockersCardiovascular effectsCrossover therapyHeart failureHypotensive effectCrossover studyChannel blockersDPP4 inhibitorsHeart rateInhibitor treatment
2016
Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition
Hubers SA, Brown NJ. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition. Circulation 2016, 133: 1115-1124. PMID: 26976916, PMCID: PMC4800749, DOI: 10.1161/circulationaha.115.018622.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, Drug-InducedAminobutyratesAngioedemaAngiotensin Receptor AntagonistsBiphenyl CompoundsBradykininContraindicationsDrug CombinationsDrug CostsDrug SynergismEnalaprilEnzyme InhibitorsFemaleFollow-Up StudiesHeart FailureHumansHyperkalemiaHypertensionKidneyMulticenter Studies as TopicNatriuretic PeptidesNeprilysinPregnancyProdrugsProspective StudiesPyridinesRandomized Controlled Trials as TopicStroke VolumeTetrazolesThiazepinesValsartanConceptsValsartan/sacubitrilReduced ejection fractionHeart failureNatriuretic peptideEjection fractionN-terminal pro-brain natriuretic peptideNeprilysin inhibitor prodrug sacubitrilPro-brain natriuretic peptideAngiotensin receptor blocker valsartanAngiotensin receptor antagonismAngiotensin receptor blockersHeart Failure TrialReceptor blocker valsartanAngiotensin receptor antagonistsBrain natriuretic peptideOngoing clinical trialsMechanism of actionNeprilysin inhibitionAldosterone antagonistsAldosterone systemReceptor blockersBlood pressureFailure TrialPathophysiological mechanismsReceptor antagonism
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
2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular level
2006
β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension
Pojoga L, Kolatkar NS, Williams JS, Perlstein TS, Jeunemaitre X, Brown NJ, Hopkins PN, Raby BA, Williams GH. β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension. Hypertension 2006, 48: 892-900. PMID: 17015767, DOI: 10.1161/01.hyp.0000244688.45472.95.Peer-Reviewed Original ResearchConceptsBlood pressure responseSalt-sensitive hypertensionBeta-2 adrenergic receptorsAldosterone secretionDietary sodiumAdrenergic receptorsGreater blood pressure responseAdrenergic receptor variantsHigh plasma aldosteroneLow plasma reninLow-sodium balanceNormotensive white subjectsMean arterial pressureLow-renin hypertensionSerum potassium levelsAdrenergic receptor genotypePressure responseBlood pressure evaluationAdrenergic receptor stimulationAldosterone responseAldosterone systemHypertensive subjectsNormotensive subjectsPlasma aldosteronePlasma renin
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 analysisSubjects
2004
Loss of Sodium Modulation of Plasma Kinins in Human Hypertension
Murphey LJ, Eccles WK, Williams GH, Brown NJ. Loss of Sodium Modulation of Plasma Kinins in Human Hypertension. Journal Of Pharmacology And Experimental Therapeutics 2004, 308: 1046-1052. PMID: 14718610, DOI: 10.1124/jpet.103.059337.Peer-Reviewed Original ResearchConceptsKallikrein-kinin systemHigh salt intakeMean arterial pressureSalt intakeAldosterone systemHypertensive subjectsUrinary kallikreinRenal kallikrein-kinin systemTissue kallikrein-kinin systemPlasma renin activityLow-salt dietUrinary kallikrein excretionSodium-retaining statesBradykinin metabolitePlasma angiotensinRenin activitySalt restrictionSodium restrictionKallikrein excretionSalt dietSerum aldosteroneArterial pressureVascular responsesHuman hypertensionSodium modulation
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 antagonistCandesartan
2002
ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism
Brown NJ, Kumar S, Painter CA, Vaughan DE. ACE Inhibition Versus Angiotensin Type 1 Receptor Antagonism. Hypertension 2002, 40: 859-865. PMID: 12468570, DOI: 10.1161/01.hyp.0000040264.15961.48.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood GlucoseBlood PressureDiureticsDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansHydrochlorothiazideHypertensionInsulinInsulin ResistanceLosartanMaleMiddle AgedPlasminogen Activator Inhibitor 1RamiprilReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSodium Chloride Symporter InhibitorsTissue Plasminogen ActivatorTreatment OutcomeConceptsPlasminogen activator inhibitor-1PAI-1 antigenAngiotensin type 1 receptor antagonismPlasma PAI-1 antigenAT1 receptor antagonismReceptor antagonismACE inhibitionAddition of ramiprilAngiotensin receptor antagonismWeeks of hydrochlorothiazideEffects of losartanPlasma PAI-1Activator inhibitor-1Aldosterone systemHypertensive subjectsBlood pressureFibrinolytic variablesMyocardial infarctionTPA antigenRisk factorsTreatment periodLosartanTPA activityAntigenInhibitor-1The 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 ResearchConceptsPlasminogen 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 pathwayDiseaseInjuryRAASSpironolactone 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
2001
Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen
Brown N, Murphey L, Srikuma N, Koschachuhanan N, Williams G, Vaughan D. Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen. Arteriosclerosis Thrombosis And Vascular Biology 2001, 21: 1071-1077. PMID: 11397722, DOI: 10.1161/01.atv.21.6.1071.Peer-Reviewed Original ResearchConceptsPAI-1 4G/5G genotypePAI-1 antigen concentrationsPAI-1 antigenHigh salt intakeLow salt intakeSalt intakeG genotypeAntigen concentrationThrombotic cardiovascular eventsPlasma renin activityPAI-1 expressionPAI-1 geneAldosterone systemCardiovascular eventsCardiovascular morbidityRenin activityPharmacological therapyEssential hypertensionSerum triglyceridesEffects of activationG polymorphismG homozygotesG groupAntigenIntake
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
1999
Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans
Brown N, Agirbasli M, Vaughan D. Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans. Hypertension 1999, 34: 285-290. PMID: 10454455, DOI: 10.1161/01.hyp.34.2.285.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin IIAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood PressureData Interpretation, StatisticalDiet, Sodium-RestrictedFemaleFibrinolysisHeart RateHumansIsoquinolinesLosartanMalePlasminogen Activator Inhibitor 1QuinaprilReninRenin-Angiotensin SystemTetrahydroisoquinolinesTissue Plasminogen ActivatorConceptsPlasminogen activator inhibitor-1PAI-1 antigenTissue plasminogen activatorACE inhibitorsFibrinolytic balanceAldosterone systemAngiotensin II type 1 receptor antagonismAngiotensin II type 1 receptor antagonistAngiotensin-Converting Enzyme InhibitionType 1 receptor antagonistPlasma PAI-1 antigenPAI-1 antigen concentrationsAntigen concentrationEquivalent hypotensive dosesPlasma fibrinolytic balancePlasma renin activityAngiotensin II formationLow salt intakePAI-1 activityClass of drugsTPA antigen concentrationsActivator inhibitor-1Enzyme inhibitionLosartan treatmentQuinapril treatment