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 polymorphismHypertension
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
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 IILoss 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
Acute 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 group
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
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 activity