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
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 variants
2011
Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis
Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ. Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis. Journal Of The American Society Of Nephrology 2011, 23: 334-342. PMID: 22158433, PMCID: PMC3269170, DOI: 10.1681/asn.2011030287.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsBlood CoagulationCD40 LigandCross-Over StudiesCytokinesDouble-Blind MethodFemaleHemodynamicsHumansInflammationKidney Failure, ChronicMaleMiddle AgedOxidative StressRamiprilRenal DialysisReninTetrazolesValineValsartanConceptsAngiotensin receptor blockersMaintenance hemodialysis patientsCardiovascular mortalityHemodialysis patientsACE inhibitorsGreater anti-inflammatory effectAngiotensin-Converting Enzyme InhibitionOxidative stressAngiotensin receptor blockadeIL-10 concentrationsD-dimer levelsIL-6 levelsProspective clinical trialsAnti-inflammatory effectsIL-1β concentrationsLevels of vWFSerial blood samplingCardiovascular eventsEndothelial dysfunctionCrossover studyWashout periodIsoprostane levelsClinical trialsDrug treatmentVWF levelsThe 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 alleleRenin gene polymorphism: its relationship to hypertension, renin levels and vascular responses
Sun B, Williams JS, Pojoga L, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Ferri C, Williams GH. Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses. Journal Of The Renin-Angiotensin-Aldosterone System 2011, 12: 564-571. PMID: 21490026, PMCID: PMC3444254, DOI: 10.1177/1470320311405873.Peer-Reviewed Original ResearchConceptsMean arterial pressurePlasma renin activityRenin activityRenin geneHypertension riskSingle nucleotide polymorphismsAngiotensin II infusionNormotensive Caucasian subjectsHyperPATH cohortII infusionPRA levelsVascular responsivenessRenin levelsArterial pressureEssential hypertensionVascular responsesAngiotensin IIHypertensionHigh riskIndependent cohortCaucasian subjectsA alleleResultant haplotypesUnderlying mechanismGene variation
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 menThe Relationship between Peroxisome Proliferator-Activated Receptor-γ and Renin: A Human Genetics Study
Underwood PC, Sun B, Williams JS, Pojoga LH, Chamarthi B, Lasky-Su J, Raby BA, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams GH. The Relationship between Peroxisome Proliferator-Activated Receptor-γ and Renin: A Human Genetics Study. The Journal Of Clinical Endocrinology & Metabolism 2010, 95: e75-e79. PMID: 20631015, PMCID: PMC2936061, DOI: 10.1210/jc.2010-0270.Peer-Reviewed Original ResearchConceptsPRA levelsPeroxisome proliferator-activated receptor gamma agonistPlasma renin activity levelsProliferator-activated receptor gamma agonistsVolume retentionAfrican-American hypertensivesHigh PRA levelsLow-salt dietRenin activity levelsAngiotensin II infusionMajor allele carriersSingle nucleotide polymorphismsC allele carrier statusReceptor gamma agonistsAllele carrier statusII infusionHypertensive participantsCombined P valueHuman hypertensionGamma agonistsNucleotide polymorphismsAllele carriersPPARgamma agonistsPPARgamma geneRenin
2009
Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome
Hill KD, Eckhauser AW, Marney A, Brown NJ. Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome. Diabetes Care 2009, 32: 857-859. PMID: 19196886, PMCID: PMC2671107, DOI: 10.2337/dc08-1862.Peer-Reviewed Original ResearchConceptsBeta-cell functionPhosphodiesterase-5 inhibitionMetabolic syndromeInsulin sensitivityPlasma renin activityDiastolic blood pressureΒ-cell functionRenin activityBlood pressureACE inhibitionAngiotensin IIFibrinolytic parametersACE activityGlucose homeostasisSeparate daysSyndromeRamiprilFibrinolysisTadalafilInhibitionTreatmentNovel strategyPlaceboResearch designWomen
2006
Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering during AT1 Receptor Blockade
LeFebvre J, Shintani A, Gebretsadik T, Petro JR, Murphey LJ, Brown NJ. Bradykinin B2 Receptor Does Not Contribute to Blood Pressure Lowering during AT1 Receptor Blockade. Journal Of Pharmacology And Experimental Therapeutics 2006, 320: 1261-1267. PMID: 17182977, DOI: 10.1124/jpet.106.117259.Peer-Reviewed Original ResearchConceptsPlasma renin activityHoe 140Endogenous bradykininReceptor blockadeBaseline plasma renin activityBlood pressure-lowering effectAT1 receptor blockadeSalt-depleted subjectsBlood pressure loweringBlood pressure responseEffect of angiotensinPressure-lowering effectAngiotensin I/Heart rate responseReceptor-independent mechanismD-Arg-ArgBradykinin B2 receptorPRA responseRenin activityChronic treatmentPlasma cGMPPressure loweringB2 receptorsEndocrine responsesHeart rate
2005
Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia
Williams JS, Williams GH, Raji A, Jeunemaitre X, Brown NJ, Hopkins PN, Conlin PR. Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia. Journal Of Human Hypertension 2005, 20: 129-136. PMID: 16292348, DOI: 10.1038/sj.jhh.1001948.Peer-Reviewed Original ResearchConceptsHigh sodium dietPrimary hyperaldosteronismModerate hypertensionSodium restrictionHypertensive populationLow serum potassium levelsNormotensive control populationSerum potassium levelsHigh blood pressureSpecific cutoff valuesElevated AERElevated ARRHaemodynamic testingNormotensive populationResistant hypertensionHypertensive subjectsNormotensive subjectsSerum aldosteroneBlood pressureEssential hypertensivesMedication washoutStudy protocolHypokalaemiaCutoff valueControl population
2004
NO Synthase Inhibition Increases Aldosterone in Humans
Muldowney JA, Davis SN, Vaughan DE, Brown NJ. NO Synthase Inhibition Increases Aldosterone in Humans. Hypertension 2004, 44: 739-745. PMID: 15381675, DOI: 10.1161/01.hyp.0000143852.48258.f1.Peer-Reviewed Original ResearchConceptsL-NAME infusionL-NAMEL-arginineAldosterone concentrationSerum potassiumNitro-L-arginine methyl esterNO precursor L-arginineEndogenous NO modulatesDouble-blind treatmentPlasma renin activityAngiotensin II concentrationEnzyme inhibitor ramiprilSystolic blood pressurePrecursor L-arginineRenin activityPlacebo pretreatmentBlood pressureSerum aldosteroneTreatment armsNO modulatesVehicle infusionHeart rateNormal subjectsSeparate daysCombined treatment
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 groupsNonmodulatorsReninComparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women
Brown NJ, Abbas A, Byrne D, Schoenhard JA, Vaughan DE. Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women. Circulation 2002, 105: 304-309. PMID: 11804984, DOI: 10.1161/hc0302.102570.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAngiotensin-Converting Enzyme InhibitorsBlood PressureCardiovascular DiseasesCross-Over StudiesDrug Therapy, CombinationEstradiolEstrogen Replacement TherapyEstrogens, Conjugated (USP)FemaleHumansMiddle AgedPlasminogen Activator Inhibitor 1Polymorphism, GeneticPostmenopauseRamiprilReninSingle-Blind MethodTissue Plasminogen ActivatorConceptsHealthy postmenopausal womenPAI-1 4G/5G genotypePlasma renin activityPostmenopausal womenPAI-1 concentrationsACE inhibitionTissue plasminogen activatorConjugated estrogensPAI-1G genotypeRenin activityAngiotensin IIPlasminogen activator inhibitor-1 (PAI-1) concentrationsAngiotensin-Converting Enzyme InhibitionPAI-1 antigen concentrationsPlasminogen activatorConjugated equine estrogensEffects of estrogenPlasminogen activator inhibitor-1Activator inhibitor-1Combination estrogenClinical outcomesEquine estrogensCombined therapyCrossover treatment
2000
Endogenous bradykinin and the renin and pressor responses to furosemide in humans.
Murphey LJ, Kumar S, Brown NJ. Endogenous bradykinin and the renin and pressor responses to furosemide in humans. Journal Of Pharmacology And Experimental Therapeutics 2000, 295: 644-8. PMID: 11046100.Peer-Reviewed Original ResearchConceptsPlasma renin activityMean arterial pressureHoe 140Renin responseEndogenous bradykininRenin activityArterial pressureHeart rateBasal plasma renin activityRenin-angiotensin systemAngiotensin I/Blood pressure regulationCrossover design studyAcute furosemide treatmentRenin regulationSpecific bradykininDiuretic responseFurosemide administrationFurosemide treatmentACE inhibitionReceptor antagonistPressure regulationBradykininFurosemideHumans
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
1998
Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1
Brown N, Agirbasli M, Williams G, Litchfield W, Vaughan D. Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1. Hypertension 1998, 32: 965-971. PMID: 9856958, DOI: 10.1161/01.hyp.32.6.965.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsCatecholaminesCircadian RhythmCreatinineDiet, Sodium-RestrictedFibrinolysisHemodynamicsHumansHydrocortisoneIsoquinolinesMalePlasminogen Activator Inhibitor 1QuinaprilReninRenin-Angiotensin SystemSodiumSupine PositionTetrahydroisoquinolinesTissue Plasminogen ActivatorConceptsLow salt intakeRenin-angiotensin systemPAI-1 antigenPlasma renin activitySalt intakeACE inhibitionMyocardial infarctionTPA antigenFibrinolytic systemPAI-1Plasminogen activator inhibitor-1 activityTissue-type plasminogen activator antigenPAI-1 antigen concentrationsPAI-1 antigen levelsThrombotic cardiovascular eventsHigh salt intakeLeft ventricular dysfunctionRecurrent myocardial infarctionPlasminogen activator antigenInhibitor-1 activityPlasma PAI-1PAI-1 activityConcomitant ACE inhibitionCardiovascular eventsRenin activityGender 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
1997
Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels
Stein C, Brown N, Carlson M, Campbell P, Wood A. Coadministration of glyburide and minoxidil, drugs with opposing effects on potassium channels. Clinical Pharmacology & Therapeutics 1997, 61: 662-668. PMID: 9209249, DOI: 10.1016/s0009-9236(97)90101-6.Peer-Reviewed Original ResearchConceptsBlood pressureHypotensive effectBlood pressure-lowering effectPotassium channelsIntravenous glucose tolerance testImportant pharmacodynamic interactionsSmall hypotensive responseDouble-blind fashionPressure-lowering effectCoadministration of drugsGlucose tolerance testSensitive potassium channelsSimilar significant decreaseBlood glucose concentrationHypotensive responsePharmacodynamic interactionsPharmacodynamic effectsSignificant hypoglycemiaHypoglycemic agentsTolerance testInsulin responseDrug interactionsHealthy subjectsHealthy volunteersHigh dose
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