2017
Two Pools of Epoxyeicosatrienoic Acids in Humans
Elijovich F, Milne GL, Brown NJ, Laniado-Schwartzman M, Laffer CL. Two Pools of Epoxyeicosatrienoic Acids in Humans. Hypertension 2017, 71: 346-355. PMID: 29279315, PMCID: PMC5764817, DOI: 10.1161/hypertensionaha.117.10392.Peer-Reviewed Original ResearchConceptsSalt-resistant subjectsDihydroxyeicosatrienoic acidsEpoxyeicosatrienoic acidsBlood pressurePlasma epoxyeicosatrienoic acidsRegulation of natriuresisSalt-sensitive subjectsUrine sodium excretionPotential therapeutic implicationsRenal poolSodium excretionInpatient protocolNormotensive subjectsFractional excretionVascular dysfunctionVascular toneSystemic originTherapeutic implicationsTotal poolNatriuresisSalt loadingExcretionUrine poolsAldosteroneCatecholamines
2013
Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension
Gilbert K, Nian H, Yu C, Luther JM, Brown NJ. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension. Journal Of Hypertension 2013, 31: 820-829. PMID: 23385647, PMCID: PMC3800119, DOI: 10.1097/hjh.0b013e32835e8227.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntihypertensive AgentsBlood PressureCross-Over StudiesDouble-Blind MethodFemaleFenofibrateHeart RateHumansMaleMiddle AgedSodium Chloride, DietaryConceptsBlood pressureSalt dietHeart ratePeroxisome proliferator-activated receptor α (PPARα) agonistSalt-resistant hypertensionPlasma renin activityRenal vascular resistanceEffect of fenofibrateLow-salt dietMean arterial pressureHigh-salt dietDouble-blind protocolTreatment of hyperlipidemiaReceptor α agonistSalt sensitivityHypertensive volunteersRenal vasoconstrictionRenin activitySodium excretionVascular resistanceArterial pressureHypertensive individualsSalt intakeSystolic pressureTreatment arms
2012
Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake
Rao AD, Sun B, Saxena A, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams JS. Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake. Journal Of Human Hypertension 2012, 27: 176-180. PMID: 22648267, PMCID: PMC3463709, DOI: 10.1038/jhh.2012.22.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkersBlood PressureChi-Square DistributionEuropeFemaleGene FrequencyGenetic Predisposition to DiseaseHumansHypertensionImmediate-Early ProteinsLinear ModelsLinkage DisequilibriumLogistic ModelsMaleMiddle AgedPhenotypePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReninRenin-Angiotensin SystemSodium Chloride, DietaryUnited StatesWhite PeopleConceptsDietary salt intakeBlood pressureSalt intakeSingle nucleotide polymorphismsHigher systolic blood pressureMeasurement of BPAldosterone system activityRAA system activitySystem activitySystolic blood pressureSalt-sensitive hypertensionSGK1 gene variantGlucocorticoid-inducible kinase 1Non-significant trendNormotensive populationRenin responseEpithelial sodium channelHuman hypertensionGenotype statusStudy populationDistal nephronHypertensionAdditive genetic modelSodium channelsGene variantsAldosterone 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 injuryLysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension
Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Chen Y, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-Specific Demethylase 1: An Epigenetic Regulator of Salt-Sensitive Hypertension. American Journal Of Hypertension 2012, 25: 812-817. PMID: 22534796, PMCID: PMC3721725, DOI: 10.1038/ajh.2012.43.Peer-Reviewed Original ResearchConceptsMinor allele carriersSalt-sensitive hypertensionBlood pressureSingle nuclear polymorphismsAllele carriersHypertensive cohortDietary saltWT miceLiberal salt dietLiberal salt intakeSystolic blood pressureSerum aldosterone concentrationHeterozygote knockout miceTranslational research studiesRenovascular responsivenessAldosterone concentrationSalt dietDietary sodiumSalt intakeSystolic BPHuman studiesHypertensionKnockout miceClinical relevanceCaucasian cohort
2011
CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow
Williams JS, Hopkins PN, Jeunemaitre X, Brown NJ. CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow. Journal Of Hypertension 2011, 29: 1913-1918. PMID: 21873888, PMCID: PMC3309034, DOI: 10.1097/hjh.0b013e32834aa786.Peer-Reviewed Original ResearchConceptsMean arterial pressureHigh salt intakeRenal blood flowHypertensive individualsBlood pressureSalt intakeC alleleSalt restrictionNormotensive individualsBlood flowSalt-sensitive blood pressureSalt sensitivityLow-salt dietDiagnosis of hypertensionHigh blood pressureSalt-sensitive hypertensionRenal vasodilationPressor responseSalt dietArterial pressureAngiotensin IIAttenuated increaseSodium homeostasisCYP4A11 T8590C polymorphismHypertensionThe Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians
Vaidya A, Sun B, Forman JP, Hopkins PN, Brown NJ, Kolatkar NS, Williams GH, Williams JS. The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians. Clinical Endocrinology 2011, 74: 783-790. PMID: 21521263, PMCID: PMC3089671, DOI: 10.1111/j.1365-2265.2011.03991.x.Peer-Reviewed Original ResearchConceptsPlasma renin activityVitamin D receptorLow plasma renin activityDietary sodium balanceRenin-angiotensin systemRenin activityFok1 polymorphismSodium balanceVitamin D receptor gene polymorphismsD receptor gene polymorphismsPopulation of hypertensivesReceptor gene polymorphismsFok1 genotypeHyperPATH cohortD deficiencyMultivariable analysisNormotensive individualsVitamin DRenin expressionVDR geneCardiovascular diseaseD receptorHuman studiesGene polymorphismsT allele
2010
Low-salt diet increases insulin resistance in healthy subjects
Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism 2010, 60: 965-968. PMID: 21036373, PMCID: PMC3036792, DOI: 10.1016/j.metabol.2010.09.005.Peer-Reviewed Original ResearchConceptsLow-salt dietHomeostasis model assessment indexModel assessment indexBody mass indexInsulin resistanceLS dietUrine aldosteroneMass indexHS dietHealthy subjectsHigher homeostasis model assessment indexUrine norepinephrine excretionPlasma renin activityHigh-salt dietSympathetic nervous systemSerum angiotensin IIPathogenesis of diabetesUrine epinephrineNorepinephrine excretionRenin activitySerum aldosteroneBlood pressureSerum sodiumAngiotensin IIHealthy men
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
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
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 II
2002
PAI-1 in human hypertension: relation to hypertensive groups*
Srikumar N, Brown NJ, Hopkins PN, Jeunemaitre X, Hunt SC, Vaughan DE, Williams GH. PAI-1 in human hypertension: relation to hypertensive groups*. American Journal Of Hypertension 2002, 15: 683-690. PMID: 12160190, DOI: 10.1016/s0895-7061(02)02952-7.Peer-Reviewed Original ResearchConceptsPlasma renin activityPAI-1 levelsPlasminogen activator inhibitor type 1Hypertensive subjectsInsulin resistanceLow reninRenin activityHigher PAI-1 levelsDietary salt restrictionLow-salt dietRenin-angiotensin systemActivator inhibitor type 1Inhibitor type 1Aldosterone levelsHypertensive groupSalt restrictionSodium dietSodium restrictionSalt dietHuman hypertensionType 1AldoModulator groupsNonmodulatorsRenin
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