2015
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial
Ramirez CE, Nian H, Yu C, Gamboa JL, Luther JM, Brown NJ, Shibao CA. Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial. The Journal Of Clinical Endocrinology & Metabolism 2015, 100: 4533-4540. PMID: 26580240, PMCID: PMC4667163, DOI: 10.1210/jc.2015-3415.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlbuminuriaDouble-Blind MethodEndothelium, VascularFemaleFibrinolysisGlucoseGlucose Clamp TechniqueGlucose Tolerance TestHemodynamicsHumansInsulinInsulin ResistanceMaleMiddle AgedOverweightPhosphodiesterase 5 InhibitorsPlasminogen Activator Inhibitor 1Prediabetic StateSildenafil CitrateConceptsPhosphodiesterase-5 inhibitionGlucose-stimulated insulin secretionInsulin sensitivity indexInsulin sensitivityInsulin secretionBaseline insulin sensitivity indexPlacebo-controlled studyClinical Research CenterBody mass indexEnd of treatmentPlasminogen activator inhibitor-1Tissue plasminogen activatorActivator inhibitor-1Placebo groupUrine albuminSildenafil groupCreatinine ratioEndothelial functionPrimary outcomeMass indexTreatment armsFibrinolytic balanceDisposition indexHyperglycemic clampOverweight individuals
2011
Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis
Gamboa JL, Pretorius M, Todd-Tzanetos DR, Luther JM, Yu C, Ikizler TA, Brown NJ. Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis. Journal Of The American Society Of Nephrology 2011, 23: 334-342. PMID: 22158433, PMCID: PMC3269170, DOI: 10.1681/asn.2011030287.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsBlood CoagulationCD40 LigandCross-Over StudiesCytokinesDouble-Blind MethodFemaleHemodynamicsHumansInflammationKidney Failure, ChronicMaleMiddle AgedOxidative StressRamiprilRenal DialysisReninTetrazolesValineValsartanConceptsAngiotensin receptor blockersMaintenance hemodialysis patientsCardiovascular mortalityHemodialysis patientsACE inhibitorsGreater anti-inflammatory effectAngiotensin-Converting Enzyme InhibitionOxidative stressAngiotensin receptor blockadeIL-10 concentrationsD-dimer levelsIL-6 levelsProspective clinical trialsAnti-inflammatory effectsIL-1β concentrationsLevels of vWFSerial blood samplingCardiovascular eventsEndothelial dysfunctionCrossover studyWashout periodIsoprostane levelsClinical trialsDrug treatmentVWF levelsRenin 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
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
2006
Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury
Ma J, Weisberg A, Griffin JP, Vaughan DE, Fogo AB, Brown NJ. Plasminogen activator inhibitor-1 deficiency protects against aldosterone-induced glomerular injury. Kidney International 2006, 69: 1064-1072. PMID: 16528256, DOI: 10.1038/sj.ki.5000201.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAldosteroneAnimalsBlood PressureChemokine CCL2CollagenFibronectinsGene ExpressionGlomerulonephritisHemodynamicsKidney GlomerulusMacrophagesMaleMiceMice, Inbred C57BLMice, Inbred StrainsMyocardiumNephrectomyOsteopontinPlasminogen Activator Inhibitor 1RNA, MessengerSialoglycoproteinsSodiumConceptsMonocyte chemoattractant protein-1Plasminogen activator inhibitor-1WT miceGlomerular injuryPlasminogen activator inhibitor-1 deficiencyCollagen IIIMRNA expressionPAI-1-deficient miceRenal collagen contentRenal osteopontin expressionSodium/potassium ratioUrine albumin excretionSystolic blood pressureRenal mRNA expressionChemoattractant protein-1Activator inhibitor-1Collagen IGrowth factor betaAlbumin excretionSodium excretionBlood pressureMesangial expansionRenal expressionCardiac injuryUrine volumeEndogenous 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
2005
A pilot study indicating that bradykinin B2 receptor antagonism attenuates protamine‐related hypotension after cardiopulmonary bypass
Pretorius M, Scholl FG, McFarlane JA, Murphey LJ, Brown NJ. A pilot study indicating that bradykinin B2 receptor antagonism attenuates protamine‐related hypotension after cardiopulmonary bypass. Clinical Pharmacology & Therapeutics 2005, 78: 477-485. PMID: 16321614, DOI: 10.1016/j.clpt.2005.08.010.Peer-Reviewed Original ResearchConceptsMean arterial pressureSaline solution groupT-PA activityAdministration of protamineCardiopulmonary bypassProtamine administrationHoe 140Receptor antagonismBradykinin concentrationsSolution groupTissue-type plasminogen activator releaseACE inhibitor-treated patientsBradykinin B2 receptor antagonismReceptor antagonist HOE 140Angiotensin-converting enzyme inhibitorB2 receptor antagonismInhibitor-treated patientsElective cardiac surgeryAdult male patientsBradykinin receptor antagonismDegradation of bradykininPlasminogen activator releaseSaline solutionProtamine infusionArterial pressureMelanocortin-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 analysisSubjects
2004
Angiotensin‐converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass
Pretorius M, McFarlane JA, Vaughan DE, Brown NJ, Murphey LJ. Angiotensin‐converting enzyme inhibition and smoking potentiate the kinin response to cardiopulmonary bypass. Clinical Pharmacology & Therapeutics 2004, 76: 379-387. PMID: 15470338, DOI: 10.1016/j.clpt.2004.06.004.Peer-Reviewed Original ResearchConceptsACE inhibitor groupMinutes of CPBCardiopulmonary bypassACE inhibitorsInhibitor groupKinin responseBradykinin concentrationsEffects of CPBCoronary artery bypass surgeryTissue-type plasminogen activator antigenPreoperative ACE inhibitorsArtery bypass surgeryPostoperative day 1Concentrations of bradykininEffect of smokingPlasminogen activator antigenKallikrein-kinin systemSignificant inverse correlationArterial pressureBypass surgeryFibrinolytic responseVenous bloodACE activityDay 1Enzyme inhibitorsNO 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 treatment
2003
Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass
Pretorius M, Murphey LJ, McFarlane JA, Vaughan DE, Brown NJ. Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass. Circulation 2003, 108: 3079-3083. PMID: 14656921, DOI: 10.1161/01.cir.0000105765.54573.60.Peer-Reviewed Original ResearchConceptsPostoperative day 1PAI-1 antigenCardiopulmonary bypassACE inhibitorsPAI-1 expressionACEI groupACE inhibitionPlasminogen activator inhibitor-1 (PAI-1) concentrationsTPA activityTissue-type plasminogen activator antigenAngiotensin-converting enzyme inhibitionAcute graft thrombosisPreoperative ACE inhibitorsMorning of surgeryCoronary artery bypassVein graft occlusionPlasminogen activator antigenArterial blood samplesArtery bypassGraft thrombosisGraft occlusionFibrinolytic responseAngiotensin IIBlood samplesDay 1Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1
Sawathiparnich P, Murphey LJ, Kumar S, Vaughan DE, Brown NJ. Effect of Combined AT1 Receptor and Aldosterone Receptor Antagonism on Plasminogen Activator Inhibitor-1. The Journal Of Clinical Endocrinology & Metabolism 2003, 88: 3867-3873. PMID: 12915681, DOI: 10.1210/jc.2003-030374.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiotensin Receptor AntagonistsBenzimidazolesBiphenyl CompoundsDiureticsElectrolytesFemaleFibrinolysisFurosemideHemodynamicsHumansMaleMineralocorticoid Receptor AntagonistsPlasminogen Activator Inhibitor 1Potassium ChlorideReceptor, Angiotensin, Type 1Renin-Angiotensin SystemSingle-Blind MethodSpironolactoneTetrazolesConceptsMean arterial pressureAldosterone receptor antagonismAng IIReceptor antagonismPAI-1Angiotensin II type 1Coadministration of spironolactoneEffects of candesartanFurosemide-induced increasePresence of candesartanAldosterone receptor antagonistsEndogenous Ang IIPlasminogen activator inhibitor-1PAI-1 antigenActivator inhibitor-1PAI-1 productionPlasminogen activator inhibitorAldosterone systemNormotensive subjectsArterial pressureAngiotensin IIAT1 receptorFibrinolytic variablesReceptor antagonistCandesartan
2002
Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Schoenhard JA, Painter CA, Ripley RT, Brown NJ, Fogo AB, Vaughan DE. Potential Roles of Plasminogen Activator System in Coronary Vascular Remodeling Induced by Long-term Nitric Oxide Synthase Inhibition. Journal Of Molecular And Cellular Cardiology 2002, 34: 617-627. PMID: 12054849, DOI: 10.1006/jmcc.2002.2001.Peer-Reviewed Original ResearchConceptsSystolic blood pressureNitric oxide synthase inhibitionOxide synthase inhibitionPerivascular fibrosisBlood pressurePAI-1 deficiencyCoronary perivascular fibrosisPlasminogen activator systemL-NAMENOS inhibitionSynthase inhibitionDeficient miceVascular pathologyLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterL-NAME-induced hypertensionLong-term NOS inhibitionPlasma TGF-beta1 levelsPlasminogen activator inhibitor-1-deficient miceStructural vascular changesTGF-beta1 levelsLong-term treatmentTissue-type plasminogen activator-deficient miceWeek study periodActivator system
2001
Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition
Kaikita K, Fogo A, Ma L, Schoenhard J, Brown N, Vaughan D. Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition. Circulation 2001, 104: 839-844. PMID: 11502712, DOI: 10.1161/hc3301.092803.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureBody WeightCollagenCoronary VesselsEnzyme InhibitorsFibrosisHemodynamicsHypertensionHypertrophy, Left VentricularMaleMiceMice, Inbred C57BLMice, KnockoutNG-Nitroarginine Methyl EsterNitric Oxide SynthasePlasminogen Activator Inhibitor 1Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerTimeConceptsPlasminogen activator inhibitor-1Systolic blood pressureLong-term NOS inhibitionBlood pressurePAI-1 deficiencyNitric oxide synthaseCoronary perivascular fibrosisPerivascular fibrosisNOS inhibitionWT miceLong-term nitric oxide synthase inhibitionNitro-L-arginine methyl esterNitric oxide synthase inhibitionWild-type male miceControl WT miceStructural vascular changesOxide synthase inhibitionArteriosclerotic cardiovascular diseaseDevelopment of fibrosisPAI-1 activityNew therapeutic strategiesActivator inhibitor-1Cardiac type ILong-term inhibitionPrevents hypertension
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
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 activityAngiotensin-Converting Enzyme Inhibitors
Brown N, Vaughan D. Angiotensin-Converting Enzyme Inhibitors. Circulation 1998, 97: 1411-1420. PMID: 9577953, DOI: 10.1161/01.cir.97.14.1411.Peer-Reviewed Original ResearchConceptsACE inhibitorsVentricular dysfunctionMyocardial infarctionAngiotensin AT1 receptor antagonistAngiotensin converting enzyme (ACE) inhibitorsTissue-bound ACESystemic vascular resistanceCongestive heart failureAT1 receptor antagonistTreatment of hypertensionRoute of eliminationVascular resistanceCardiovascular mortalityDiabetic nephropathyEssential hypertensionHeart failureNatriuretic propertiesRenal diseaseVasoactive substancesAngiotensin IIReceptor antagonistHeart rateSide effectsEnzyme inhibitorsHypertrophic properties