2010
Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice
Kreiger M, Di Lorenzo A, Teutsch C, Kauser K, Sessa WC. Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice. Laboratory Investigation 2010, 90: 1573-1581. PMID: 20585312, PMCID: PMC3248785, DOI: 10.1038/labinvest.2010.116.Peer-Reviewed Original ResearchConceptsCav-1 KO miceAngiotensin receptor blockersKO miceCardiac functionLV hypertrophyWT miceCardiac hypertrophyΒ-myosin heavy chainBody weight ratioTibial length ratioNatriuretic peptide ACaveolin-1-deficient miceCav-1 KOReceptor blockersPerivascular fibrosisVentricular hypertrophyVentricular weightAngiotensin IIIntramyocardial vesselsSpontaneous modelUnique genetic modelHypertrophyMiceTreatmentCaveolin-1
2000
In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation
Bucci M, Gratton J, Rudic R, Acevedo L, Roviezzo F, Cirino G, Sessa W. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nature Medicine 2000, 6: 1362-1367. PMID: 11100121, DOI: 10.1038/82176.Peer-Reviewed Original ResearchConceptsCaveolin-1Signal transductionSmall-molecule mimicryCaveolae assemblyInternalization sequenceCoat proteinEndothelial cellsPhysiological importanceEndothelial nitric oxide synthase (eNOS) inhibitorTransductionCholesterol transportNitric oxide synthase inhibitorChimeric peptideInhibits nitric oxide synthesisOxide synthase inhibitorNitric oxide synthesisNew therapeutic approachesNitric oxide productionSelective inhibitionDomainPeptidesCaveolinAcute inflammationCellsSystemic administrationThe HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer D, Sessa W, Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Medicine 2000, 6: 1004-1010. PMID: 10973320, PMCID: PMC2828689, DOI: 10.1038/79510.Peer-Reviewed Original ResearchConceptsProtein kinase Akt/PKBKinase Akt/PKBProtein kinase AktAkt/PKBAkt-dependent mannerVascular structure formationActivation of AktKinase AktVascular endothelial growth factor treatmentEnhanced phosphorylationBlood vessel growthNew blood vessel growthAktGrowth factor treatmentVessel growthEndothelial cellsEndothelial nitric oxide synthaseRecent studiesHMG-CoA reductase inhibitor simvastatinAngiogenesisPKBFactor treatmentPhosphorylationReductase inhibitor simvastatinApoptosisGeldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo
Bucci M, Roviezzo F, Cicala C, Sessa W, Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti‐inflammatory effects and interacts with glucocorticoid receptor in vivo. British Journal Of Pharmacology 2000, 131: 13-16. PMID: 10960063, PMCID: PMC1572305, DOI: 10.1038/sj.bjp.0703549.Peer-Reviewed Original ResearchConceptsAnti-inflammatory effectsAnti-inflammatory actionEdema formationRU 486Heat shock protein 90Shock protein 90Endothelial nitric oxide synthaseEndothelium-dependent relaxationAnti-inflammatory dosePotential anti-inflammatory drugsVascular endothelial growth factorNitric oxide synthaseAnti-inflammatory drugsEndothelial growth factorDose-dependent mannerProtein 90Specific inhibitorIntact blood vesselsIntraplantar administrationPaw edemaMiddle arteryOxide synthaseRat aortaTherapeutic rationaleGlucocorticoid receptorTemporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice
Rudic R, Bucci M, Fulton D, Segal S, Sessa W. Temporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice. Circulation Research 2000, 86: 1160-1166. PMID: 10850968, DOI: 10.1161/01.res.86.11.1160.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarotid Artery, CommonCell DeathDrug CombinationsIn Vitro TechniquesMaleMiceMice, Inbred C57BLMuscle, Smooth, VascularNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRegional Blood FlowTime FactorsTunica MediaVasodilator AgentsVasomotor SystemConceptsLeft common carotid arteryRight common carotid arteryCommon carotid arteryCarotid arteryBlood flowLeft external carotid arteryEndothelial NO synthase (eNOS) functionEndothelial NO synthase (eNOS) mRNAExternal carotid arteryNO synthase mRNANitrovasodilator sodium nitroprussideAcute ligationEndothelial dysfunctionArterial remodelingControl arteriesVascular remodelingAdult miceSodium nitroprussideDay 7Structural remodelingArteryLuminal remodelingMarked reductionProtein levelsMice
1999
Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension
Shah V, Wiest R, Garcia-Cardena G, Cadelina G, Groszmann R, Sessa W. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension. American Journal Of Physiology 1999, 277: g463-g468. PMID: 10444461, DOI: 10.1152/ajpgi.1999.277.2.g463.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAnimalsBenzoquinonesBlood VesselsHSP90 Heat-Shock ProteinsHypertension, PortalIn Vitro TechniquesLactams, MacrocyclicMaleMethoxamineMicrocirculationNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIQuinonesRatsRats, Sprague-DawleySplanchnic CirculationTissue DistributionVasoconstrictor AgentsVasodilationVasodilator AgentsConceptsEndothelial nitric oxide synthasePortal vein ligationNitric oxide synthasePortal hypertensionMesenteric vasculatureOxide synthaseNormal animalsACh-dependent vasodilationExperimental portal hypertensionExcessive NO productionNO-dependent responsesNOS catalytic activityDependent vasodilationVein ligationVascular controlMesenteric circulationPVL animalsMesenteric vesselsHeat shock protein 90Sodium nitroprussideNO productionEndothelial liningHypertensionShock protein 90MethoxamineNO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats
Wiest R, Shah V, Sessa W, Groszmann R. NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. American Journal Of Physiology 1999, 276: g1043-g1051. PMID: 10198349, DOI: 10.1152/ajpgi.1999.276.4.g1043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Flow VelocityBlood PressureEndothelium, VascularHypertension, PortalKineticsLuminescent MeasurementsMaleMesenteric Artery, SuperiorMethoxamineNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroarginineRatsRats, Sprague-DawleySplanchnic CirculationStress, MechanicalConceptsHyperdynamic splanchnic circulationSuperior mesenteric arterySplanchnic circulationSham ratsNitric oxide synthase upregulationHyperdynamic circulatory syndromeNO metabolites concentrationPortal hypertensive ratsENOS protein levelsHigh blood flowSignificant hyporesponsivenessArterial vasodilatationL-NNAPortal hypertensionPVL ratsAgonist methoxamineCirculatory syndromeENOS upregulationHypertensive ratsMesenteric arteryNomega-nitroNO inhibitorBlood flowDay 3L-arginine
1998
Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling
Papapetropoulos A, Piccardoni P, Cirino G, Bucci M, Sorrentino R, Cicala C, Johnson K, Zachariou V, Sessa W, Altieri D. Hypotension and inflammatory cytokine gene expression triggered by factor Xa–nitric oxide signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 4738-4742. PMID: 9539808, PMCID: PMC22560, DOI: 10.1073/pnas.95.8.4738.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelium, VascularFactor XaFibrinogenGene Expression RegulationHistamineHumansHypotensionInflammationInterleukin-6MaleNG-Nitroarginine Methyl EsterNitric OxidePolymerase Chain ReactionRatsRats, WistarSplanchnic CirculationStereoisomerismTumor Necrosis Factor-alphaUmbilical VeinsConceptsEffector cell protease receptor-1Cytokine gene expressionFactor XaReceptor 1NO synthase inhibitor LNitric oxideInflammatory cytokine gene expressionActivation of coagulationNitroarginine methyl esterEndothelial cell releaseTissue factor pathway inhibitorAcute phase responseEndothelial cell ligandsThrombin inhibitor hirudinInterleukin-6 mRNAFactor pathway inhibitorDose-dependent mannerVascular endothelial cellsL-NAMED-NAMEGrowth factor peptidesInterleukin-6Dose-dependent reactionCell ligandsPathway inhibitor
1996
Nitric oxide synthase induction with renal transplant rejection or infection
Smith S, Wheeler M, Zhang R, Weiss E, Lorber M, Sessa W, Weiss R. Nitric oxide synthase induction with renal transplant rejection or infection. Kidney International 1996, 50: 2088-2093. PMID: 8943494, DOI: 10.1038/ki.1996.533.Peer-Reviewed Original ResearchConceptsUrinary tract infectionRenal transplant patientsNitric oxide synthaseCyclic GMP levelsTransplant patientsTract infectionsNOS activityPost-renal transplantation patientsGMP levelsInducible nitric oxide synthaseNitric oxideRenal allograft rejectionRenal transplant rejectionNitric oxide synthase inductionInducible NOS (iNOS) mRNAUrine of patientsRenal transplantationTransplantation patientsAllograft rejectionTransplant rejectionInducible NOSOxide synthaseNOS mRNAPatientsSynthase inductionElevated blood pressures in mice lacking endothelial nitric oxide synthase
Shesely E, Maeda N, Kim H, Desai K, Krege J, Laubach V, Sherman P, Sessa W, Smithies O. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 13176-13181. PMID: 8917564, PMCID: PMC24066, DOI: 10.1073/pnas.93.23.13176.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBlood PressureCattleChimeraDNA PrimersEndothelium, VascularFemaleGenotypeHeterozygoteHypertensionIsoenzymesKidneyLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutNitric Oxide SynthasePolymerase Chain ReactionReninRNA, MessengerStem CellsTranscription, GeneticConceptsEndothelial nitric oxide synthaseBlood pressureNitric oxide synthaseHeart rateENOS proteinOxide synthaseENOS mutant miceLipopolysaccharide-induced deathElevated blood pressureNormal blood pressurePlasma renin concentrationBlood pressure regulationLower body weightKidney renin mRNAAnti-eNOS antibodiesAppropriate genetic controlsENOS locusENOS genotypesRenin concentrationVascular toneFemale miceRenin mRNAENOS geneENOS mutationBody weight
1993
20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries
Escalante B, Omata K, Sessa W, Lee S, Falck J, Schwartzman M. 20-Hydroxyeicosatetraenoic acid is an endothelium-dependent vasoconstrictor in rabbit arteries. European Journal Of Pharmacology 1993, 235: 1-7. PMID: 8519270, DOI: 10.1016/0014-2999(93)90812-v.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicArachidonic AcidCarotid ArteriesCattleCells, CulturedDose-Response Relationship, DrugEndothelium, VascularHydroxyeicosatetraenoic AcidsIn Vitro TechniquesMaleMesenteric ArteriesProstaglandin-Endoperoxide SynthasesRabbitsRenal ArteryVasoconstrictionVasoconstrictor AgentsConceptsBlood vesselsEndothelium-dependent vasoconstrictorEndothelial cyclooxygenaseRegulation of hemostasisVasoconstrictor metabolitesContractile potencyContractile effectAortic ringsVascular tonePlatelet functionMuscular arteriesRabbit arteriesArachidonate metabolitesPlatelet aggregationCyclooxygenaseArachidonic acidArteryBlood cellsRabbit kidneySeminal vesiclesEicosatetraenoic acidMajor arachidonate metabolitePotencyRam seminal vesiclesPresent study
1992
High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis
Murch SH, Braegger CP, MacDonald T, Sessa W. High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis. The Lancet 1992, 339: 381-385. PMID: 1346658, DOI: 10.1016/0140-6736(92)90077-g.Peer-Reviewed Original ResearchConceptsCrohn's disease patientsInflammatory bowel diseaseDisease patientsUlcerative colitisCrohn's diseaseBowel diseaseEndothelin-1Lamina propriaChronic inflammatory bowel diseaseEndothelin-1 immunoreactivitySubmucosal blood vesselsUlcerative colitis patientsTissue samplesUlcerative colitis groupEndothelin concentrationsImmunological hypersensitivityIntestinal ischaemiaColitis groupColitis patientsEndothelin productionInflammatory cellsPotent vasoconstrictorVascular abnormalitiesDisease groupImmunoreactive cells
1991
Human Polymorphonuclear Leukocytes Generate and Degrade Endothelin-1 by Two Distinct Neutral Proteases
Sessa W, Kaw S, Zembowicz A, Änggård E, Hecker M, Vane J. Human Polymorphonuclear Leukocytes Generate and Degrade Endothelin-1 by Two Distinct Neutral Proteases. Journal Of Cardiovascular Pharmacology 1991, 17: s34-38. PMID: 1725374, DOI: 10.1097/00005344-199100177-00010.Peer-Reviewed Original ResearchConceptsET-1Big endothelinEndothelin-1Important pathophysiologic implicationsHuman polymorphonuclear leukocytesFMLP-activated PMNHuman big endothelinContractile factorsPMN infiltrationLeukocyte cathepsin GContractile activityPathophysiologic implicationsActivated PMNsPolymorphonuclear leukocytesNeutral proteaseDisease statesCell-free supernatantCathepsin GPMNPhosphoramidonMetabolism
1990
L-Glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta
Swierkosz T, Mitchell J, Sessa W, Hecker M, Vane J. L-Glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta. Biochemical And Biophysical Research Communications 1990, 172: 143-148. PMID: 2222463, DOI: 10.1016/s0006-291x(05)80184-6.Peer-Reviewed Original ResearchConceptsRelease of EDRFRabbit aortic stripsAortic stripsRabbit aortaL-arginineL-ArgACh-induced relaxationEndothelium-dependent relaxationL-GlnL-Arg levelsIntact blood vesselsEDRF biosynthesisAortic tissueConsecutive infusionsEDRFL-glutamineAortaEndothelial cellsInitial equilibration periodBlood vesselsD-ArgInhibitory effectInfusionPresent studyAmino acid L-glutamineCytochrome P450-Dependent Arachidonic Acid Metabolites, 19− and 20-Hydroxyeicosatetraenoic Acids, Enhance Sodium-Potassium ATPase Activity in Vascular Smooth Muscle
Escalante B, Sessa W, Falck JR, Yadagiri P, Schwartzman M. Cytochrome P450-Dependent Arachidonic Acid Metabolites, 19− and 20-Hydroxyeicosatetraenoic Acids, Enhance Sodium-Potassium ATPase Activity in Vascular Smooth Muscle. Journal Of Cardiovascular Pharmacology 1990, 16: 438-443. PMID: 1700215, DOI: 10.1097/00005344-199009000-00013.Peer-Reviewed Original ResearchConceptsCytochrome P450-dependent arachidonic acid metabolitesPotassium-induced relaxationArachidonic acid metabolitesAcid metabolitesOuabain-sensitive 86Rb uptakeSodium-potassium ATPase activityRat aortic ringsProstaglandin-like materialVascular smooth muscleDose-dependent fashionEffect of omegaAortic ringsSmooth muscleStimulatory effectInhibitory effectATPase activityPresent studyMetabolitesCyclooxygenaseIndomethacinRelease of a neutrophil‐derived vascoconstrictor agent which augments platelet‐induced contractions of blood vessels in vitro
Sessa W, Mullane K. Release of a neutrophil‐derived vascoconstrictor agent which augments platelet‐induced contractions of blood vessels in vitro. British Journal Of Pharmacology 1990, 99: 553-559. PMID: 2110018, PMCID: PMC1917347, DOI: 10.1111/j.1476-5381.1990.tb12967.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicBlood PlateletsCalcimycinIn Vitro TechniquesLipoxygenase InhibitorsMaleMolecular WeightMuscle ContractionMuscle TonusMuscle, Smooth, VascularNeutrophilsN-Formylmethionine Leucyl-PhenylalanineRabbitsSerotoninSerotonin AntagonistsTetradecanoylphorbol AcetateVasoconstrictor AgentsConceptsContractile factorsVascular toneBlood vesselsEnd-organ antagonistNeutrophil-derived productsPlatelet-induced contractionsConcentration-dependent contractionsInhibition of contractionRat stomach stripCyclo-oxygenase enzymeTimes more plateletsRabbit thoracic aortaPhorbol myristate acetateFree radical scavengerContractile responseInhibitors of lipoxygenaseOrgan bathAngiotensin IIReceptor antagonistStomach stripIntact endotheliumNeutrophil activationThoracic aortaActivated neutrophilsDesArg9-bradykininStz-Induced Diabetes in Shr and Renovascular Hypertensive Rats: Dissociation Between Changes in Arterial Pressure and Vascular Collagen Synthesis
Mariani M, Sessa W, Chichester C, Rodgers R. Stz-Induced Diabetes in Shr and Renovascular Hypertensive Rats: Dissociation Between Changes in Arterial Pressure and Vascular Collagen Synthesis. Clinical And Experimental Hypertension 1990, 12: 1003-1019. PMID: 2245511, DOI: 10.3109/10641969009073514.Peer-Reviewed Original ResearchConceptsRenovascular hypertensive ratsVascular collagen synthesisArterial pressureHypertensive ratsCollagen synthesisSTZ induced diabetesLeft renal arteryNormotensive WKY ratsSTZ-induced diabetesWistar-Kyoto ratsNondiabetic SHRRVH ratsRenovascular hypertensionWKY controlsNormotensive controlsRenal arteryWKY ratsProlyl hydroxylase activitySHRDiabetesRatsHydroxylase activityProline incorporationHypertensionWKY
1987
Myocardial Salvage Induced by REV-5901
Mullane K, Hatala M, Kraemer R, Sessa W, Westlin W. Myocardial Salvage Induced by REV-5901. Journal Of Cardiovascular Pharmacology 1987, 10: 398-406. PMID: 2444792, DOI: 10.1097/00005344-198710000-00004.Peer-Reviewed Original ResearchConceptsCoronary artery occlusionArtery occlusionInfarct sizeEnd-organ antagonistLeukotriene-like materialAccumulation of neutrophilsLeukotriene B4 generationSelective cyclooxygenase inhibitorsLeukotriene B4 formationSpasmogenic effectNeutrophil accumulationHemodynamic effectsHypoperfused zoneMyocardial injuryMyocardial salvageCardiac damageIschemic myocardiumB4 generationAnesthetized dogsCyclooxygenase inhibitorIschemic heartB4 formationCyclooxygenase enzymesCanine neutrophilsLipoxygenase metabolites