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 ResearchConceptsBlood 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
2011
The 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 alleleAldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonismRenin 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 men
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
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
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 rateEndogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition
Brown NJ, Muldowney JA, Vaughan DE. Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition. Hypertension 2006, 47: 441-448. PMID: 16432054, DOI: 10.1161/01.hyp.0000202478.79587.1a.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsArginineDouble-Blind MethodDrug CombinationsEnzyme InhibitorsFemaleFibrinolysisHemodynamicsHumansInfusions, IntravenousMaleMiddle AgedNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthasePlasminogen Activator Inhibitor 1ProdrugsRamiprilReference ValuesRenin-Angiotensin SystemConceptsPlasminogen activator inhibitor-1Plasminogen activator inhibitor-1 antigenActivator inhibitor-1Salt-replete subjectsL-arginineFibrinolytic balanceInhibitor-1Angiotensin-Converting Enzyme InhibitionNO precursor L-argininePlasminogen activator inhibitor antigenTissue-type plasminogen activator antigenEffect of angiotensinPrecursor L-argininePlasminogen activator antigenNO synthase inhibitorEnzyme inhibitionT-PA activityRenin activityD-dimerInhibitor antigenNormal subjectsSynthase inhibitorEnzyme inhibitorsT-PAAntigen
2004
Uric 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 activityNO 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 treatmentLoss 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
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
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
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
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 activityEffect 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 responseGender 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
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