2018
DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition
Hubers SA, Wilson JR, Yu C, Nian H, Grouzmann E, Eugster P, Shibao CA, Billings FT, Jafarian Kerman S, Brown NJ. DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition. Hypertension 2018, 72: 712-719. PMID: 29987109, PMCID: PMC6202157, DOI: 10.1161/hypertensionaha.118.11498.Peer-Reviewed Original ResearchConceptsNPY infusionPlacebo-controlled crossover studyAngiotensin-converting enzyme inhibitorAldosterone system inhibitionDose-dependent vasoconstrictionIntra-arterial enalaprilatAngiotensin receptor blockersForearm blood flowHigh-risk patientsOrder of treatmentReceptor blockersVasoconstrictor effectVasoconstrictor responsesCardiovascular effectsRenin-AngiotensinBrachial arteryHeart failureNorepinephrine releaseCrossover studyEndogenous NPYY1 receptorCrossover treatmentSystem inhibitionY2 receptorsDPP4 inhibition
2014
Dipeptidyl‐Peptidase 4 Inhibition and the Vascular Effects of Glucagon‐like Peptide‐1 and Brain Natriuretic Peptide in the Human Forearm
Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ. Dipeptidyl‐Peptidase 4 Inhibition and the Vascular Effects of Glucagon‐like Peptide‐1 and Brain Natriuretic Peptide in the Human Forearm. Journal Of The American Heart Association 2014, 3: e001075. PMID: 25158865, PMCID: PMC4310400, DOI: 10.1161/jaha.114.001075.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1Brain natriuretic peptideForearm blood flowNatriuretic peptideDPP4 inhibitionBlood flowPeptide-1Placebo-controlled crossover studyDipeptidyl peptidase-4 inhibitorsDipeptidyl peptidase-4 inhibitionForearm vascular resistanceDose-dependent vasodilationMean arterial pressureGLP-1 concentrationsHuman forearmSitagliptin useDirect vasodilatorVascular resistanceVasodilator responseVascular effectsArterial pressureBrachial arteryDiabetes mellitusGlycemic controlNorepinephrine releaseSubstance P Increases Sympathetic Activity During Combined Angiotensin-Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition
Devin JK, Pretorius M, Nian H, Yu C, Billings FT, Brown NJ. Substance P Increases Sympathetic Activity During Combined Angiotensin-Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition. Hypertension 2014, 63: 951-957. PMID: 24516103, PMCID: PMC3984385, DOI: 10.1161/hypertensionaha.113.02767.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininCross-Over StudiesDipeptidyl Peptidase 4Double-Blind MethodEnalaprilatEnzyme InhibitorsFemaleHeart RateHumansMaleMiddle AgedNeurotransmitter AgentsNorepinephrinePeptidyl-Dipeptidase APyrazinesSitagliptin PhosphateSubstance PSympathetic Nervous SystemTriazolesVascular ResistanceConceptsDipeptidyl peptidase-4 inhibitionPeptidase-4 inhibitionTissue plasminogen activator releaseSubstance PDipeptidyl peptidase-4Plasminogen activator releaseSympathetic activityPeptidase-4Activator releasePlacebo-controlled crossover studyDipeptidyl peptidase-4 inhibitorsType 2 diabetes mellitusIntra-arterial enalaprilatForearm vascular resistanceForearm blood flowMean arterial pressurePeptidase-4 inhibitorsAngiotensin converting enzymeSubstrates of angiotensinVascular resistanceVasodilator responseArterial pressureBrachial arteryDiabetes mellitusCrossover study
2012
Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans
Marczak ED, Marzec J, Zeldin DC, Kleeberger SR, Brown NJ, Pretorius M, Lee CR. Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. Pharmacogenetics And Genomics 2012, 22: 620-628. PMID: 22668754, PMCID: PMC3599320, DOI: 10.1097/fpc.0b013e32835516e5.Peer-Reviewed Original ResearchConceptsForearm vascular resistanceForearm blood flowVariant allele carriersVasodilator responseSodium nitroprussideVascular functionAllele carriersStrain-gauge venous occlusion plethysmographyLower forearm blood flowEndothelial-independent mannerForearm vasodilator responseVenous occlusion plethysmographyWild-type individualsTranscription factor Nrf2Endothelial dysfunctionOcclusion plethysmographyVascular resistanceIncremental dosesCardiovascular diseaseBlood flowG genotypeA polymorphismSignificant associationBasal conditionsFactor Nrf2
2010
Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans
Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans. Hypertension 2010, 57: 116-122. PMID: 21098312, PMCID: PMC3020911, DOI: 10.1161/hypertensionaha.110.161695.Peer-Reviewed Original ResearchConceptsForearm blood flowVariant allele carriersForearm vasodilator responseForearm vascular resistanceSoluble epoxide hydrolaseVascular resistanceVasodilator responseBlood flowAllele carriersSodium nitroprussideVascular functionStrain-gauge venous occlusion plethysmographyHighest forearm blood flowLower forearm vascular resistanceSignificant associationCytochrome P450-derived epoxyeicosatrienoic acidsEpoxide hydrolaseVenous occlusion plethysmographyCardiovascular disease riskEndothelium-independent mannerWild-type individualsOcclusion plethysmographyPotent vasodilatorEpoxyeicosatrienoic acidsPreclinical modelsIncreased 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
2009
Endogenous Nitric Oxide Contributes to Bradykinin-Stimulated Glucose Uptake but Attenuates Vascular Tissue-Type Plasminogen Activator Release
Pretorius M, Brown NJ. Endogenous Nitric Oxide Contributes to Bradykinin-Stimulated Glucose Uptake but Attenuates Vascular Tissue-Type Plasminogen Activator Release. Journal Of Pharmacology And Experimental Therapeutics 2009, 332: 291-297. PMID: 19841473, PMCID: PMC2802470, DOI: 10.1124/jpet.109.160168.Peer-Reviewed Original ResearchConceptsT-PA releaseNet t-PA releaseForearm blood flowTissue-type plasminogen activator releaseL-NMMANitric oxide synthasePlasminogen activator releaseGlucose uptakeActivator releaseBaseline forearm blood flowBaseline forearm vascular resistanceArterial-venous gradientEndogenous NO contributesForearm vascular resistanceNitric oxide contributesIntra-arterial bradykininMonomethyl-L-arginineMuscle glucose uptakeCyclooxygenase inhibitor aspirinEndogenous nitric oxide contributesGender-stratified analysesVascular resistanceNondiabetic subjectsNOS inhibitionFibrinolytic response
2008
17&bgr;-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women
Pretorius M, van Guilder GP, Guzman RJ, Luther JM, Brown NJ. 17&bgr;-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women. Hypertension 2008, 51: 1190-1196. PMID: 18259028, PMCID: PMC2673569, DOI: 10.1161/hypertensionaha.107.105627.Peer-Reviewed Original ResearchConceptsYounger postmenopausal womenT-PA antigenEffect of angiotensinPostmenopausal womenT-PA releaseActive t-PAT-PAAntigen releasePlasminogen activator inhibitor-1 antigenTissue-type plasminogen activator releaseNet t-PA releaseForearm blood flowPlasminogen activator releaseEnzyme inhibitionCrossover studyIntraarterial infusionBasal releaseVascular releaseTreatment periodFibrinolytic functionPlaceboBlood flowActivator releaseAngiotensinAntigenBradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition
Van Guilder GP, Pretorius M, Luther JM, Byrd JB, Hill K, Gainer JV, Brown NJ. Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition. Hypertension 2008, 51: 454-459. PMID: 18180402, PMCID: PMC2581632, DOI: 10.1161/hypertensionaha.107.102574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininDrug SynergismEnalaprilatEndothelium, VascularFemaleForearmGenotypeHumansInjections, Intra-ArterialMaleMethacholine ChlorideNitroprussidePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowSex FactorsTissue Plasminogen ActivatorVascular ResistanceVasodilationVasodilator AgentsConceptsForearm blood flowT-PA releaseForearm vascular resistanceVascular resistanceBlood flowBlood pressureTissue-type plasminogen activator releaseBasal forearm blood flowAngiotensin-Converting Enzyme InhibitionGenotype groupsNet t-PA releaseReceptor-mediated vasodilationBasal forearm vascular resistanceSystolic blood pressureBody mass indexIntra-arterial bradykininEffect of bradykininDegradation of bradykininPlasminogen activator releaseEnzyme inhibitionMass indexVascular responsesActivator releaseBradykininWhite American subjects
2006
Bradykinin and Its Metabolite Bradykinin 1-5 Inhibit Thrombin-Induced Platelet Aggregation in Humans
Murphey LJ, Malave HA, Petro J, Biaggioni I, Byrne DW, Vaughan DE, Luther JM, Pretorius M, Brown NJ. Bradykinin and Its Metabolite Bradykinin 1-5 Inhibit Thrombin-Induced Platelet Aggregation in Humans. Journal Of Pharmacology And Experimental Therapeutics 2006, 318: 1287-1292. PMID: 16772538, DOI: 10.1124/jpet.106.104026.Peer-Reviewed Original ResearchConceptsForearm blood flowNet t-PA releaseT-PA releaseThrombin-induced platelet aggregationPlatelet aggregationBradykinin 1Thrombin receptor-activating peptide-induced platelet aggregationTissue plasminogen activator antigenMajor stable metabolitePeptide-induced platelet aggregationDoses of bradykininThrombin receptor-activating peptideAntecubital venous bloodPlasminogen activator antigenArterial plasma samplesDose-dependent increaseGamma-thrombinReceptor-activating peptidePlatelet-rich plasmaPmol/minPeptide infusionBrachial arteryVenous bloodHealthy subjectsBlood flow
2005
Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men
Pretorius M, Luther JM, Murphey LJ, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men. Arteriosclerosis Thrombosis And Vascular Biology 2005, 25: 2435-2440. PMID: 16166566, DOI: 10.1161/01.atv.0000186185.13977.94.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininEnalaprilatFemaleHumansLuteal PhaseMaleMethacholine ChlorideMiddle AgedNitroprussideParasympathomimeticsPeptide FragmentsPeptidyl-Dipeptidase APostmenopausePremenopauseRegional Blood FlowSex CharacteristicsTissue Plasminogen ActivatorVasodilator AgentsConceptsT-PA releaseForearm blood flowBasal t-PA releaseNet t-PA releaseTissue plasminogen activator releasePostmenopausal womenPlasminogen activator releaseOlder menPremenopausal womenMenopausal statusActivator releaseIntra-arterial enalaprilatEffect of ACEIEndogenous bradykininHormone replacementExogenous bradykininBlood flowACEIBradykininEnalaprilatWomenYoung menMenEnzyme inhibitionRelease
2004
Relationship Between Carbamoyl-Phosphate Synthetase Genotype and Systemic Vascular Function
Summar ML, Gainer JV, Pretorius M, Malave H, Harris S, Hall LD, Weisberg A, Vaughan DE, Christman BW, Brown NJ. Relationship Between Carbamoyl-Phosphate Synthetase Genotype and Systemic Vascular Function. Hypertension 2004, 43: 186-191. PMID: 14718356, DOI: 10.1161/01.hyp.0000112424.06921.52.Peer-Reviewed Original ResearchConceptsForearm blood flowNitric oxide metabolite concentrationsNitric oxide metabolitesBlood flowOxide metabolitesNitric oxide-mediated vasodilationVascular smooth muscle reactivityAllele homozygotesTissue-type plasminogen activator antigenSystemic vascular functionSmooth muscle reactivityPlasminogen activator antigenC allele homozygotesNitric oxide productionMetabolite concentrationsVasodilator responseBrachial arteryMuscle reactivityVascular functionHealthy subjectsBlood samplesSodium nitroprussideC alleleOxide productionCarbamoyl phosphate synthetase 1
2003
Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin
Pretorius M, Rosenbaum D, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin. Circulation 2003, 107: 579-585. PMID: 12566370, DOI: 10.1161/01.cir.0000046268.59922.a4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin-Converting Enzyme InhibitorsBlood Flow VelocityBradykininBradykinin Receptor AntagonistsDose-Response Relationship, DrugEnalaprilatEndothelium, VascularFemaleFibrinolysisForearmHumansInfusions, Intra-ArterialMaleMethacholine ChlorideMuscarinic AgonistsRegional Blood FlowSmokingTissue Plasminogen ActivatorVascular ResistanceConceptsForearm blood flowNet t-PA releaseT-PA releaseEndothelial t-PA releaseHoe 140T-PA responseEndogenous bradykininACE inhibitionExogenous bradykininTissue-type plasminogen activator releaseReceptor antagonist HOE 140Angiotensin-Converting Enzyme InhibitionBradykinin receptor antagonist HOE 140Effects of enalaprilatIntra-arterial enalaprilatIntra-arterial infusionPlasminogen activator releaseEnzyme inhibitionFBF responseVascular resistanceBlood flowActivator releaseEnalaprilatBradykininMethacholine
2002
Ethnicity Affects Vasodilation, but Not Endothelial Tissue Plasminogen Activator Release, in Response to Bradykinin
Rosenbaum DA, Pretorius M, Gainer JV, Byrne D, Murphey LJ, Painter CA, Vaughan DE, Brown NJ. Ethnicity Affects Vasodilation, but Not Endothelial Tissue Plasminogen Activator Release, in Response to Bradykinin. Arteriosclerosis Thrombosis And Vascular Biology 2002, 22: 1023-1028. PMID: 12067915, DOI: 10.1161/01.atv.0000017704.45007.1d.Peer-Reviewed Original ResearchConceptsForearm blood flowFibrinolytic functionSodium nitroprussideEffect of ethnicityAge-matched normotensive subjectsTissue plasminogen activator antigenTissue plasminogen activator releaseDoses of bradykininPlasminogen activator antigenPlasminogen activator releaseFBF responseVasodilator responseNormotensive subjectsBrachial arteryIndependent agonistsArterial samplesBlood flowAntigen releaseActivator releaseBradykininMethacholineAcetylcholineWhite AmericansNitroprussideBlack AmericansSmoking Impairs Bradykinin-Stimulated t-PA Release
Pretorius M, Rosenbaum DA, Lefebvre J, Vaughan DE, Brown NJ. Smoking Impairs Bradykinin-Stimulated t-PA Release. Hypertension 2002, 39: 767-771. PMID: 11897760, DOI: 10.1161/hy0302.105767.Peer-Reviewed Original ResearchConceptsTissue plasminogen activator releaseTissue plasminogen activator responsePlasminogen activator releaseForearm blood flowDose-dependent increaseActivator releaseBlood flowDoses of nitroprussideSignificant dose-dependent increaseActivator responseStrain-gauge plethysmographyBody mass indexEffect of bradykininT-PA releaseReceptor-dependent mechanismEndothelial functionBrachial arteryMass indexMethacholineSmokersNonsmokersBradykininHuman endotheliumRandom orderSignificant differences
2001
Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm
Wilsdorf T, Gainer J, Murphey L, Vaughan D, Brown N. Angiotensin-(1-7) Does Not Affect Vasodilator or TPA Responses to Bradykinin in Human Forearm. Hypertension 2001, 37: 1136-1140. PMID: 11304515, DOI: 10.1161/01.hyp.37.4.1136.Peer-Reviewed Original ResearchConceptsForearm blood flowAng IBlood flowTissue plasminogen activator responseTPA releaseAng I infusionDoses of AngHuman forearm vasculatureEffects of AngPeripheral vascular resistanceSystemic hemodynamic effectsRole of AngNormotensive subjectsVascular resistanceVasoconstrictor responsesVasodilator effectHemodynamic effectsBrachial arteryForearm vasculatureI infusionACE inhibitionSupraphysiological dosesRat modelConstant infusionAngInteractive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity
Gainer JV, Stein CM, Neal T, Vaughan DE, Brown NJ. Interactive Effect of Ethnicity and ACE Insertion/Deletion Polymorphism on Vascular Reactivity. Hypertension 2001, 37: 46-51. PMID: 11208755, DOI: 10.1161/01.hyp.37.1.46.Peer-Reviewed Original ResearchACE insertion/deletion polymorphismGreater vasodilator responseVasodilator responseACE D alleleSodium nitroprussideInsertion/deletion polymorphismVascular reactivityEndothelium-independent vasodilator sodium nitroprussideD allelePotent endothelium-dependent vasodilatorVascular smooth muscle reactivityACE I/D genotypeEffect of angiotensinForearm blood flowSmooth muscle reactivityEndothelium-dependent vasodilatorVasodilator sodium nitroprussideDeletion polymorphismTreatment of hypertensionACE gene locusVascular sensitivityNormotensive subjectsNormotensive blacksVenous plethysmographyBlood pressure
2000
Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B2 Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway
Brown N, Gainer J, Murphey L, Vaughan D. Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B2 Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway. Circulation 2000, 102: 2190-2196. PMID: 11056091, DOI: 10.1161/01.cir.102.18.2190.Peer-Reviewed Original ResearchMeSH Keywords6-Ketoprostaglandin F1 alphaAcetylcholineAdrenergic beta-AntagonistsAdultBradykininBradykinin Receptor AntagonistsCyclooxygenase InhibitorsEndothelium, VascularFemaleForearmHumansIndomethacinInfusions, Intra-ArterialMaleNitric Oxide SynthaseNitroprussideOmega-N-MethylargininePlethysmographyReceptor, Bradykinin B2Regional Blood FlowTissue Plasminogen ActivatorVasodilationVasodilator AgentsConceptsTissue plasminogen activator releaseVasodilator responseL-NMMAPlasminogen activator releaseCyclooxygenase-independent pathwayTPA releaseActivator releaseBasal forearm blood flowReceptor antagonist HOE 140NO synthase inhibitor LHuman endotheliumHuman forearm vasculatureForearm blood flowEffect of indomethacinIntra-arterial bradykininReceptor-dependent effectsCyclooxygenase inhibitor indomethacinMonomethyl-L-arginineForearm vasodilationEndothelial effectsIndomethacin administrationForearm vasculatureHoe 140Receptor antagonismUrinary excretion
1999
Bradykinin Stimulates Tissue Plasminogen Activator Release in Human Vasculature
Brown N, Gainer J, Stein C, Vaughan D. Bradykinin Stimulates Tissue Plasminogen Activator Release in Human Vasculature. Hypertension 1999, 33: 1431-1435. PMID: 10373228, DOI: 10.1161/01.hyp.33.6.1431.Peer-Reviewed Original ResearchConceptsForearm blood flowPlasminogen activator inhibitor antigenTissue plasminogen activator releaseDose-dependent increasePlasminogen activator releaseTPA releaseInhibitor antigenBlood flowActivator releaseMean arterial pressureStrain-gauge plethysmographyHuman vasculatureInfused armNormotensive volunteersArterial pressureVasodilator nitroprussidePlasma levelsTPA antigenHeart rateSystemic effectsSodium nitroprussideAcetylcholineBradykininNitroprussideRandom order
1998
Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature
Stein C, Brown N, Vaughan D, Lang C, Wood A. Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature. Journal Of The American College Of Cardiology 1998, 32: 117-122. PMID: 9669258, DOI: 10.1016/s0735-1097(98)00210-1.Peer-Reviewed Original ResearchConceptsT-PA releaseTissue-type plasminogen activator releaseAdministration of isoproterenolSodium nitroprussidePlasminogen activator releaseVascular endotheliumActivator releasePAI-1Local t-PA releaseAdministration of SNPT-PA antigen levelsNet t-PA releasePlasma t-PA levelsEndothelium-independent agonistsForearm plasma flowNitric oxide agonistsForearm blood flowBeta-adrenoceptor agonistsVenous blood samplesRisk of thrombosisT-PA levelsEnzyme-linked immunosorbent assayPlasminogen activator inhibitorNormotensive menBrachial artery