2010
Increased 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
2007
Acute 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
Endogenous 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
Aldosterone and end-organ damage
Brown NJ. Aldosterone and end-organ damage. Current Opinion In Nephrology & Hypertension 2005, 14: 235-241. PMID: 15821416, DOI: 10.1097/01.mnh.0000165889.60254.98.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptor antagonismCongestive heart failureHeart failureReceptor antagonismMineralocorticoid receptorOxidative stressMineralocorticoid receptor-dependent mechanismEndothelial nitric oxide synthaseContribution of aldosteroneEnd-organ damageReceptor-independent effectsMineralocorticoid receptor agonistRecent clinical studiesInduction of inflammationNitric oxide synthaseRapid nongenomic mechanismsReceptor-dependent mechanismExtracellular matrix turnoverMineralocorticoid antagonismInflammatory markersCardiovascular mortalityEndothelial dysfunctionRenal injuryEndothelial functionRenal disease
2004
NO 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 treatmentEstablished and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events
Ridker PM, Brown NJ, Vaughan DE, Harrison DG, Mehta JL. Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events. Circulation 2004, 109: iv-6-iv-19. PMID: 15226246, DOI: 10.1161/01.cir.0000133444.17867.56.Peer-Reviewed Original ResearchEnvironmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I
Summar ML, Hall L, Christman B, Barr F, Smith H, Kallianpur A, Brown N, Yadav M, Willis A, Eeds A, Cermak E, Summar S, Wilson A, Arvin M, Putnam A, Wills M, Cunningham G. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Molecular Genetics And Metabolism 2004, 81: 12-19. PMID: 15050969, DOI: 10.1016/j.ymgme.2003.11.014.Peer-Reviewed Original ResearchRelationship 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
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