2010
Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans
Marney A, Kunchakarra S, Byrne L, Brown NJ. Interactive Hemodynamic Effects of Dipeptidyl Peptidase-IV Inhibition and Angiotensin-Converting Enzyme Inhibition in Humans. Hypertension 2010, 56: 728-733. PMID: 20679179, PMCID: PMC3305047, DOI: 10.1161/hypertensionaha.110.156554.Peer-Reviewed Original ResearchMeSH KeywordsAdultAldosteroneAngiotensin-Converting Enzyme InhibitorsBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Dipeptidyl Peptidase 4Dose-Response Relationship, DrugDouble-Blind MethodDrug InteractionsDrug Therapy, CombinationEnalaprilFemaleHeart RateHemodynamicsHumansInsulinMaleMetabolic SyndromeMiddle AgedPeptidyl-Dipeptidase AProspective StudiesPyrazinesRenal CirculationSitagliptin PhosphateSodiumTriazolesConceptsDipeptidyl peptidase IV inhibitionACE inhibitionHypotensive responseHemodynamic effectsBlood pressureHeart rateSerum dipeptidyl peptidase IV activityAngiotensin-Converting Enzyme InhibitionAcute ACE inhibitionVasoconstrictor neuropeptide YBlood pressure responseRenal blood flowSympathetic nervous systemType 2 diabeticsCross-over fashionDipeptidyl peptidase IV inhibitorsDose-dependent effectDipeptidyl peptidase IV activityDose-dependent mannerPeptidase IV inhibitorsPeptidase IV activityMetabolic syndromeNorepinephrine concentrationsIncretin hormonesNeuropeptide Y
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
2007
The Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance
Pretorius MM, Gainer JV, Van Guilder GP, Coelho EB, Luther JM, Fong P, Rosenbaum DD, Malave HA, Yu C, Ritchie MD, Vaughan DE, Brown NJ. The Bradykinin Type 2 Receptor BE1 Polymorphism and Ethnicity Influence Systolic Blood Pressure and Vascular Resistance. Clinical Pharmacology & Therapeutics 2007, 83: 122-129. PMID: 17522594, DOI: 10.1038/sj.clpt.6100250.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlack or African AmericanBlood Flow VelocityBlood PressureBradykininDose-Response Relationship, DrugFemaleForearmGene FrequencyGenotypeHumansInfusions, Intra-ArterialMaleNitroprussidePhenotypePolymorphism, GeneticReceptor, Bradykinin B2Regional Blood FlowVascular ResistanceVasodilator AgentsWhite PeopleConceptsSystolic blood pressureForearm vascular resistanceVascular resistanceBlood pressureEndothelium-independent agonist sodium nitroprussideEndothelium-dependent agonist bradykininIntrabrachial artery infusionsLeft ventricular massBradykinin B2 receptor geneB2 receptor geneNormotensive subjectsVentricular massPulse pressureB2 receptorsAgonist bradykininSodium nitroprussideReceptor geneBradykininGroupPolymorphismInfusionWhite AmericansNitroprussideBaselineBlack AmericansAcute tissue-type plasminogen activator release in human microvascular endothelial cells: The roles of Gαq, PLC-β, IP3 and 5,6-epoxyeicosatrienoic acid
Muldowney JA, Painter CA, Sanders-Bush E, Brown NJ, Vaughan DE. Acute tissue-type plasminogen activator release in human microvascular endothelial cells: The roles of Gαq, PLC-β, IP3 and 5,6-epoxyeicosatrienoic acid. Thrombosis And Haemostasis 2007, 97: 263-271. PMID: 17264956, DOI: 10.1160/th05-02-0092.Peer-Reviewed Original ResearchMeSH Keywords8,11,14-Eicosatrienoic AcidAortaBiological FactorsCell ProliferationCells, CulturedDose-Response Relationship, DrugEndothelial CellsEpoprostenolGTP-Binding Protein alpha Subunits, Gq-G11HumansInositol 1,4,5-TrisphosphateIsoenzymesMicrocirculationNitric OxidePhospholipase C betaPotassiumSignal TransductionThrombinTime FactorsTissue Plasminogen ActivatorType C PhospholipasesUmbilical VeinsConceptsT-PA releaseHuman microvascular endothelial cellsMicrovascular endothelial cellsEpoxyeicosatrienoic acidsTissue-type plasminogen activatorTissue-type plasminogen activator releaseEndothelial cellsIP3 receptor antagonistCalcium signalingT-PA antigenRole of GαqPlasminogen activator releaseMS-PPOHPhysiologic releaseCytochrome P450 inhibitorsL-NAMEEET antagonistReceptor antagonistActivator releaseVascular homeostasisNitric oxideProstacyclinPlasminogen activatorEET-methyl esterMicroM concentration
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 ResearchMeSH KeywordsAdultBradykininDose-Response Relationship, DrugFemaleFetusFibrinolysisHumansMalePeptide FragmentsPlasminogen Activator Inhibitor 1Platelet AggregationPlatelet Aggregation InhibitorsThrombinConceptsForearm 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
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 individuals
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
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-1Smoking 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
2000
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Modulates the Human In Vivo Metabolism of Bradykinin
Murphey L, Gainer J, Vaughan D, Brown N. Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Modulates the Human In Vivo Metabolism of Bradykinin. Circulation 2000, 102: 829-832. PMID: 10952948, DOI: 10.1161/01.cir.102.8.829.Peer-Reviewed Original ResearchMeSH KeywordsAdultAllelesBrachial ArteryBradykininDose-Response Relationship, DrugFemaleGenotypeHumansInfusions, Intra-ArterialMalePeptide FragmentsPeptidyl-Dipeptidase APolymorphism, GeneticTissue Plasminogen ActivatorConceptsPlasma ACE activityACE activityInsertion/deletion polymorphismD genotypeD alleleBK1-5ACE I/D polymorphismEnzyme insertion/deletion polymorphismAngiotensin-Converting Enzyme Insertion/Deletion PolymorphismTissue plasminogen activator releaseAngiotensin II productionDeletion polymorphismTissue ACE activityACE D alleleACE I/IPlasminogen activator releaseFmol/mLPlasma ACE levelsBradykinin metabolismBrachial arteryVenous returnCardioprotective peptideKinin concentrationsACE levelsBradykinin concentrationsInhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans.
Kim KS, Kumar S, Simmons WH, Brown NJ. Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans. Journal Of Pharmacology And Experimental Therapeutics 2000, 292: 295-8. PMID: 10604961.Peer-Reviewed Original ResearchConceptsDegradation of bradykininACE inhibitionWheal responseACE inhibitor quinaprilEffect of quinaprilNon-ACE pathwaysMetabolism of bradykininDose-response curveCardioprotective effectsIntradermal administrationIntradermal injectionOral administrationHealthy subjectsEnzyme inhibitorsSignificant interactionQuinaprilBradykininAminopeptidase PAngiotensinInhibitionAdministrationHuman skinPresent studyApstatinResponse
1999
Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema
Blais C, Rouleau J, Brown N, Lepage Y, Spence D, Munoz C, Friborg J, Geadah D, Gervais N, Adam A. Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema. Immunopharmacology 1999, 43: 293-302. PMID: 10596866, DOI: 10.1016/s0162-3109(99)00133-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngioedemaAngiotensin-Converting Enzyme InhibitorsBradykininDose-Response Relationship, DrugFemaleHalf-LifeHumansLysine CarboxypeptidaseMaleMiddle AgedConceptsDes-Arg9AE patientsC subjectsLife-threatening adverse reactionsEnzyme (ACE) inhibitor-associated angioedemaMetabolism of bradykininLocal inflammatory reactionEnzyme defectPreincubation of seraBK metabolismSensitive enzyme immunoassayB1 agonistSerum metabolismAdverse reactionsControl subjectsInflammatory reactionACEIAngioedemaAbnormal metabolismPatientsEnzyme inhibitorsSynthetic bradykininControl seraBradykininEnzyme immunoassay
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 arteryGender 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
1991
A pharmacodynamic interaction between caffeine and phenylpropanolamine
Brown N, Ryder D, Branch R. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clinical Pharmacology & Therapeutics 1991, 50: 363-371. PMID: 1914371, DOI: 10.1038/clpt.1991.152.Peer-Reviewed Original ResearchConceptsBlood pressurePharmacodynamic interactionsPlasma renin activityRenin-angiotensin systemDrug-free subjectsCoadministration of caffeineRenin responseRenin activityPharmacokinetic interactionsCatecholamine levelsSupine positionNormal subjectsLatin square design studyDrug AdministrationRandom orderPhenylpropanolamineMetabolite levelsPlaceboCaffeineSubjectsAdditive increaseHoursCoadministrationEpinephrineAdministration