2010
Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism
Fong P, Stafforini DM, Brown NJ, Pretorius M. Increased blood flow induces oxidative stress through an endothelium- and nitric oxide-independent mechanism. Free Radical Biology And Medicine 2010, 49: 301-305. PMID: 20423727, PMCID: PMC2916026, DOI: 10.1016/j.freeradbiomed.2010.04.023.Peer-Reviewed Original ResearchConceptsForearm blood flowHypertensive subjectsL-NMMAIsoprostane releaseBlood flowOxidative stressBasal forearm blood flowNitric oxide-independent mechanismEndothelium-independent mechanismNO synthase inhibitorEffect of bradykininMonomethyl-L-arginineIntraarterial bradykininPotent vasodilatorSynthase inhibitionSynthase inhibitorBradykininNitric oxideDependent mechanismReactive oxygen speciesHuman vasculatureSignificant increaseNitroprussideSubjectsOxygen species
2008
The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension
Laffer CL, Gainer JV, Waterman MR, Capdevila JH, Laniado-Schwartzman M, Nasjletti A, Brown NJ, Elijovich F. The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Hypertension 2008, 51: 767-772. PMID: 18227405, PMCID: PMC2365894, DOI: 10.1161/hypertensionaha.107.102921.Peer-Reviewed Original ResearchConceptsBlood pressureC carriersHypertensive subjectsSalt-sensitive hypertensive subjectsHigher diastolic blood pressureT8590C polymorphismSalt-sensitive subjectsDiastolic blood pressureMicroU/mLDahl S ratsSerum insulin concentrationsC allele carriersC allele frequencySalt sensitivityPressure natriuresisEssential hypertensionFractional excretionSerum insulinHip ratioHuman hypertensionInsulin resistanceInsulin sensitivitySodium balanceInsulin concentrationsTT subjects
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
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 populationMelanocortin-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 analysisSubjectsSingle nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension
King LM, Gainer JV, David GL, Dai D, Goldstein JA, Brown NJ, Zeldin DC. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenetics And Genomics 2005, 15: 7-13. PMID: 15864120, DOI: 10.1097/01213011-200501000-00002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesArginineAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C8Cytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemElectrolytesFemaleGenotypeHumansHypertensionLinkage DisequilibriumLysineMaleMiddle AgedOdds RatioOxygenasesPharmacogeneticsPolymorphism, GeneticPolymorphism, Single NucleotideRiskSex FactorsConceptsFamily historyVariant allele frequencyCaucasian maleGenotype distributionVariant allelesArachidonic acidRisk of hypertensionBody mass indexAdditional subgroup analysesAfrican AmericansCis-epoxyeicosatrienoic acidsBiethnic populationNormotensive CaucasiansHypertensive subjectsAllele frequenciesMass indexVascular toneHypertension riskHypertension statusSubgroup analysisOdds ratioHypertensionProtective effectCYP2C8 geneCYP2J2
2004
Thyroid Function and Blood Pressure Homeostasis in Euthyroid Subjects
Gumieniak O, Perlstein TS, Hopkins PN, Brown NJ, Murphey LJ, Jeunemaitre X, Hollenberg NK, Williams GH. Thyroid Function and Blood Pressure Homeostasis in Euthyroid Subjects. The Journal Of Clinical Endocrinology & Metabolism 2004, 89: 3455-3461. PMID: 15240631, DOI: 10.1210/jc.2003-032143.Peer-Reviewed Original ResearchConceptsMean arterial pressureRenal vascular resistanceBlood pressure homeostasisBaseline mean arterial pressureEffective renal plasma flowRenal plasma flowPressure homeostasisThyroid functionVascular resistanceEuthyroid subjectsBlood pressure salt sensitivitySalt sensitivityBlood pressure responseSystemic vascular resistanceAminohippuric acid clearanceLow sodium dietBody mass indexBaseline characteristicsHypertensive subjectsNormotensive subjectsSubclinical hypothyroidismArterial pressureAcid clearanceMass indexEuthyroid individualsLoss 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
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-1PAI-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 groupsNonmodulatorsReninSpironolactone 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-1Dipeptidyl Peptidase IV Activity in Patients With ACE-Inhibitor-Associated Angioedema
Lefebvre J, Murphey LJ, Hartert TV, Jiao Shan R, Simmons WH, Brown NJ. Dipeptidyl Peptidase IV Activity in Patients With ACE-Inhibitor-Associated Angioedema. Hypertension 2002, 39: 460-464. PMID: 11882590, DOI: 10.1161/hy0202.103054.Peer-Reviewed Original ResearchConceptsDPPIV activityHypertensive volunteersHypertensive subjectsRemote historyAcute ACE inhibitionSerum DPPIV activityUntreated hypertensive controlsUntreated hypertensive subjectsMetabolism of bradykininDipeptidyl peptidase IV activityAcute ACEIChronic ACEiPeptidase IV activityCorticosteroid treatmentHypertensive controlsHypertensive patientsNormotensive volunteersNormotensive controlsACE inhibitorsACE inhibitionSubstance PBradykinin degradationAssociated angioedemaACEIAngioedema
2000
Human β2‐adrenergic receptor polymorphisms: No association with essential hypertension in black or white Americans
Xie H, Stein C, Kim R, Gainer J, Sofowora G, Dishy V, Brown N, Goree R, Haines J, Wood A. Human β2‐adrenergic receptor polymorphisms: No association with essential hypertension in black or white Americans. Clinical Pharmacology & Therapeutics 2000, 67: 670-675. PMID: 10872649, DOI: 10.1067/mcp.2000.106293.Peer-Reviewed Original ResearchConceptsHypertensive subjectsEssential hypertensionGlu27 alleleBeta2-adrenergic receptor genotypesBeta2-adrenergic receptor polymorphismsWhite subjectsReceptor variantsBeta2-adrenergic receptor geneNormotensive white subjectsPresence of hypertensionBlack subjectsHomozygous genotypeBeta2-adrenergic receptorCommon genetic polymorphismsHypertensive groupNormotensive subjectsBlood pressurePopulation-based case-control association studiesVascular responsesCase-control association studyReceptor polymorphismsReceptor genotypeHypertensionReceptor responsesHuman beta2-adrenergic receptor
1998
Effect of Bradykinin-Receptor Blockade on the Response to Angiotensin-Converting–Enzyme Inhibitor in Normotensive and Hypertensive Subjects
Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of Bradykinin-Receptor Blockade on the Response to Angiotensin-Converting–Enzyme Inhibitor in Normotensive and Hypertensive Subjects. New England Journal Of Medicine 1998, 339: 1285-1292. PMID: 9791144, DOI: 10.1056/nejm199810293391804.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsBlood PressureBradykininBradykinin Receptor AntagonistsCaptoprilDiet, Sodium-RestrictedDrug InteractionsDrug Therapy, CombinationFemaleHumansHypertensionKidneyLosartanMaleReference ValuesRenin-Angiotensin SystemSingle-Blind MethodConceptsPlasma renin activityBlood pressureACE inhibitionHypertensive subjectsShort-term effectsRenin activitySpecific bradykinin receptor antagonistAngiotensin converting enzyme (ACE) inhibitorsAdministration of captoprilAdministration of losartanBradykinin receptor blockadeCoadministration of icatibantContribution of bradykininRenal hemodynamic responseNormal blood pressureRenin-angiotensin systemSeparate study daysBradykinin receptor antagonistDegradation of bradykininAntagonist losartanHypertensive personsHypotensive effectAngiotensin IIAngiotensin-ConvertingHemodynamic response