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
2008
Endogenous 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-1
2007
Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency
Brown NJ, Bradford J, Wang Z, Lea W, Ma L, Ma J, Vaughan DE, Fogo AB. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney International 2007, 72: 72-81. PMID: 17429342, DOI: 10.1038/sj.ki.5002268.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsAortaBlood PressureGene Expression RegulationKidneyLiverLosartanMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNorepinephrinePlasminogen Activator Inhibitor 1Random AllocationReceptor, Angiotensin, Type 1RNA, MessengerVasoconstrictor AgentsConceptsPAI-1 expressionPlasminogen activator inhibitor-1 expressionSystolic blood pressureAng IIBlood pressureReceptor deficiencyWT miceAngiotensin IIBaseline systolic blood pressureAT1a receptor deficiencyEffects of losartanReceptor knockout micePressor responseWT heartsReceptor mRNAKnockout miceLosartanNorepinephrinePAI-1AortaKidneyLiverMiceCell-type specificHeart
2004
Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling
Weisberg AD, Albornoz F, Griffin JP, Crandall DL, Elokdah H, Fogo AB, Vaughan DE, Brown NJ. Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 Attenuates Angiotensin II/Salt-Induced Aortic Remodeling. Arteriosclerosis Thrombosis And Vascular Biology 2004, 25: 365-371. PMID: 15576638, DOI: 10.1161/01.atv.0000152356.85791.52.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAdministration, OralAngiotensin IIAnimalsAntigens, DifferentiationAortaAortic DiseasesBlood PressureChemokine CCL2Collagen Type ICollagen Type IIIDrug Evaluation, PreclinicalFibronectinsFibrosisGene Expression RegulationGlomerulosclerosis, Focal SegmentalHeartHypertrophy, Left VentricularIndoleacetic AcidsIndolesKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1Random AllocationRNA, MessengerSialoglycoproteinsSingle-Blind MethodSodium Chloride, DietaryConceptsAng IIAortic remodelingCardiac fibrosisPAI-039PAI-1 inhibitionVascular remodelingCardiac hypertrophyMouse modelHeart/body weight ratioAng II/saltWall thickeningPharmacological inhibitionSmall molecule PAI-1 inhibitorAortic mRNA expressionHigh salt intakeAortic wall thickeningMale C57BL/6J miceBody weight ratioChemoattractant protein-1PAI-1 deficiencyPAI-1 activityPAI-1 inhibitorPlasminogen activator inhibitorPressor responseAngiotensin IIUric acid and the state of the intrarenal renin-angiotensin system in humans
Perlstein TS, Gumieniak O, Hopkins PN, Murphey LJ, Brown NJ, Williams GH, Hollenberg NK, Fisher ND. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney International 2004, 66: 1465-1470. PMID: 15458439, DOI: 10.1111/j.1523-1755.2004.00909.x.Peer-Reviewed Original ResearchConceptsIntrarenal renin-angiotensin systemRenin-angiotensin systemSerum uric acid concentrationBody mass indexHigh-density lipoproteinUric acid concentrationRenal vascular responsePlasma renin activityAng IIRPF responseExperimental hyperuricemiaBlood pressureVascular responsesUric acidRenal plasma flow responsePara-aminohippuric acid clearanceHigh sodium balanceIntrarenal RAS activityRenal vascular responsivenessExogenous angiotensin IISerum high-density lipoproteinSerum uric acidMultivariable regression analysisPlasma flow responseRenin activity
2003
Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice
Eren M, Painter CA, Gleaves LA, Schoenhard JA, Atkinson JB, Brown NJ, Vaughan DE. Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice. Journal Of Thrombosis And Haemostasis 2003, 1: 2389-2396. PMID: 14629474, DOI: 10.1046/j.1538-7836.2003.00437.x.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsGene Expression RegulationGreen Fluorescent ProteinsHumansImmunohistochemistryLipopolysaccharidesLuminescent ProteinsMiceMice, TransgenicOrgan SpecificityPlasminogen Activator Inhibitor 1Promoter Regions, GeneticTissue DistributionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsTranscriptional responseMurine PAI-1Plasminogen activator inhibitor-1 promoterPhysiological regulationPAI-1 promoterPlasminogen activator inhibitor type 1 (PAI-1) expressionGreen fluorescent proteinAgonist-specific regulationTranscription factorsTransgenic strategiesTransgenic miceDNA sequencesPAI-1 expressionHeterologous promoterAng IIQuantitative regulationRegulatory mechanismsRegulatory factorsFluorescent proteinKb promoterTransgenic animalsPhysiological relevancePromoterFunctional studiesEGFP expressionAcute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives
Murphey LJ, Morrow JD, Sawathiparnich P, Williams GH, Vaughan DE, Brown NJ. Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives. Free Radical Biology And Medicine 2003, 35: 711-718. PMID: 14583335, DOI: 10.1016/s0891-5849(03)00395-2.Peer-Reviewed Original ResearchConceptsF2-isoprostane concentrationsMean arterial pressurePlasma F2-isoprostane concentrationsAng II infusionAng IIII infusionOxidative stressF2-isoprostanesAcute Ang II infusionMin ANG IIPlasma renin activityHigh salt intakeLow salt intakeRenin-angiotensin systemLow sodium dietAngiotensin II increasesBody mass indexRenal plasma flowPlasma F2-isoprostanesHuman cardiovascular diseaseHuman hypertensivesHypertensive volunteersHypertensive groupHypertensive humansNormotensive groupEffect 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
2000
Synergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production1
Brown N, Kim K, Chen Y, Blevins L, Nadeau J, Meranze S, Vaughan D. Synergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production1. The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 336-344. PMID: 10634408, DOI: 10.1210/jcem.85.1.6305.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAdrenal GlandsAldosteroneAngiotensin IIAnimalsBlotting, NorthernCells, CulturedChromosome MappingDexamethasoneGenes, ReporterHumansHydrocortisoneHyperaldosteronismMuscle, Smooth, VascularMutagenesis, Site-DirectedPlasminogen Activator Inhibitor 1RatsTissue Plasminogen ActivatorTransfectionConceptsPAI-1 expressionAng IIEffects of aldosteroneAngiotensin IIVenous bloodTissue plasminogen activator antigenPAI-1 antigen concentrationsSelective adrenal veinHuman PAI-1 promoterL Ang IIPeripheral venous bloodRat aortic smooth muscle cellsAdrenal venous bloodPlasminogen activator antigenAortic smooth muscle cellsPlasminogen activator inhibitor-1 productionCultured human umbilical vein endothelial cellsPlasminogen activator inhibitor expressionPAI-1 antigenSmooth muscle cellsHuman umbilical vein endothelial cellsDose-dependent mannerUmbilical vein endothelial cellsL aldosteroneAdrenal vein
1998
ACE Insertion/Deletion Genotype Affects Bradykinin Metabolism
Brown N, Blais C, Gandhi S, Adam A. ACE Insertion/Deletion Genotype Affects Bradykinin Metabolism. Journal Of Cardiovascular Pharmacology 1998, 32: 373-377. PMID: 9733349, DOI: 10.1097/00005344-199809000-00006.Peer-Reviewed Original ResearchConceptsSerum ACE activityAng IIACE activityPlasma Ang II concentrationACE insertion/deletion genotypeACE deletion alleleAng I infusionAng II concentrationsDeleterious cardiovascular effectsACE D alleleInsertion/deletion genotypeSignificant inverse relationACE deletionCardiovascular morbidityCardiovascular effectsI infusionAng IACE genotypeACE levelsACE DDBradykinin degradationAngiotensin ID alleleSynthetic bradykininDeletion alleleGender Affects Renal Vasoconstrictor Response to Ang I and Ang II
Gandhi S, Gainer J, King D, Brown N. Gender Affects Renal Vasoconstrictor Response to Ang I and Ang II. Hypertension 1998, 31: 90-96. PMID: 9449397, DOI: 10.1161/01.hyp.31.1.90.Peer-Reviewed Original ResearchConceptsRenal vasoconstrictor responsesAng II levelsAng IAng IIVasoconstrictor responsesPressor responseII levelsHeart rateAng I infusionPlasma renin activityAng II infusionBaseline blood pressureMean arterial pressureAng II concentrationsRenal plasma flowII infusionRenin activitySodium excretionAngiotensin infusionNormotensive subjectsArterial pressureBlood pressureCrossover studyI infusionACE activity
1996
Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans.
Gandhi S, Ryder D, Brown N. Losartan blocks aldosterone and renal vascular responses to angiotensin II in humans. Hypertension 1996, 28: 961-6. PMID: 8952583, DOI: 10.1161/01.hyp.28.6.961.Peer-Reviewed Original ResearchConceptsRenal plasma flow responseExogenous Ang IIRenal plasma flowBaseline renal plasma flowPara-aminohippurate clearanceAng IIAldosterone levelsPlasma flow responseAngiotensin IIAng II type 1 receptor blockadeAng II type 1 receptorFlow responseBaseline plasma aldosterone levelsType 1 receptor blockadeII type 1 receptorAng II doseBaseline systolic pressureRenal vascular responseAng II infusionEffects of losartanPlasma aldosterone levelsSystolic pressure responseType 1 receptorAbsence of losartanPmol/L
1993
Caffeine attenuates the renal vascular response to angiotensin II infusion.
Brown NJ, Ryder D, Nadeau J. Caffeine attenuates the renal vascular response to angiotensin II infusion. Hypertension 1993, 22: 847-852. PMID: 8244516, DOI: 10.1161/01.hyp.22.6.847.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal GlandsAldosteroneAnalysis of VarianceAngiotensin IIBlood PressureCaffeineCreatinineDose-Response Relationship, DrugDrug AntagonismHumansInfusions, IntravenousMetabolic Clearance RateP-Aminohippuric AcidPotassiumRenal CirculationReninSingle-Blind MethodSodiumSodium Chloride, DietaryConceptsRenal plasma flowRenal plasma flow responsePara-aminohippurate clearancePlasma renin activityAngiotensin II infusionAng IIII infusionPlasma flow responseRenin activityBlood pressureEndogenous adenosineShort-term angiotensin II infusionBaseline plasma renin activityBaseline renal plasma flowTissue Ang II levelsAdenosine receptor antagonist caffeineRenal vascular responseRenal vasoconstrictive responseAng II levelsAng II infusionBaseline blood pressureBlood pressure responsePlacebo-controlled studyLong-term administrationTissue adenosine levels