2012
Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury
Luther JM, Luo P, Wang Z, Cohen SE, Kim HS, Fogo AB, Brown NJ. Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II–induced cardiac, renal, and vascular injury. Kidney International 2012, 82: 643-651. PMID: 22622494, PMCID: PMC3434275, DOI: 10.1038/ki.2012.170.Peer-Reviewed Original ResearchMeSH KeywordsAldosteroneAngiotensin IIAnimalsAortaBiomarkersBlood PressureCytochrome P-450 CYP11B2Disease Models, AnimalFibrosisGene Expression RegulationHeart DiseasesInflammationKidney DiseasesKidney GlomerulusMiceMice, 129 StrainMice, Inbred C57BLMineralocorticoid Receptor AntagonistsMyocardiumReceptors, MineralocorticoidRenin-Angiotensin SystemSodium Chloride, DietarySpironolactoneTime FactorsVascular DiseasesConceptsMineralocorticoid receptor antagonismAbsence of aldosteroneAldosterone deficiencyAngiotensin IIReceptor antagonismMineralocorticoid receptorKnockout miceAldosterone synthase knockout (AS(-/-)) miceMineralocorticoid receptor antagonist spironolactonePlasminogen activator inhibitor-1 mRNA expressionAldosterone synthase inhibitionMineralocorticoid receptor activationPrevents angiotensin IIAngiotensin II treatmentSynthase knockout miceBlood urea nitrogenWild-type miceWild-type littermatesMineralocorticoid antagonismAntagonist spironolactoneAortic remodelingRenal injuryEndogenous aldosteroneGlomerular hypertrophyGlomerular injury
2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular level
2010
Aldosterone and inflammation
Gilbert KC, Brown NJ. Aldosterone and inflammation. Current Opinion In Endocrinology Diabetes And Obesity 2010, 17: 199-204. PMID: 20422780, PMCID: PMC4079531, DOI: 10.1097/med.0b013e3283391989.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptorAngiotensin subtype 1 receptorAldosterone-induced inflammationMineralocorticoid receptor activationVascular collagen depositionMineralocorticoid receptor antagonistsSubtype 1 receptorInflammatory cell infiltrationVascular smooth muscle cellsAldosterone synthase inhibitorsNuclear factor-kappaBSmooth muscle cellsCell-specific effectsInflammatory phenotypeReceptor antagonistTissue inflammationCell infiltrationTherapeutic roleCollagen depositionSynthase inhibitorAldosteroneFactor-kappaBInflammationReceptor activationMuscle cells
2006
Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor–Dependent Mechanism
Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, Brown NJ. Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor–Dependent Mechanism. Hypertension 2006, 48: 1050-1057. PMID: 17043157, DOI: 10.1161/01.hyp.0000248135.97380.76.Peer-Reviewed Original ResearchConceptsMineralocorticoid receptor-dependent mechanismAngiotensin IIReceptor-dependent mechanismBlood pressureIL-6Normotensive subjectsCrossover studyHigh-sensitivity C-reactive proteinSerum IL-6 concentrationDouble-blind crossover studyOxidative stressWeeks of placeboIL-6 concentrationsC-reactive proteinRenal plasma flowIntravenous aldosteroneAldosterone responseSerum potassiumInterleukin-6Mineralocorticoid receptorPlaceboAldosteroneSpironolactoneSeparate daysReceptor independent
2005
Aldosterone and end-organ damage
Brown N. Aldosterone and end-organ damage. Current Opinion In Internal Medicine 2005, 4: 381-387. DOI: 10.1097/00132980-200508000-00009.Peer-Reviewed Original ResearchMineralocorticoid 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 mechanismPurpose of reviewExtracellular matrix turnoverMineralocorticoid antagonismInflammatory markersCardiovascular mortalityEndothelial dysfunctionRenal injuryEndothelial functionAldosterone 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