Angiotensin-Converting Enzyme 2 Over-Expression in the Central Nervous System Reduces Angiotensin-II-Mediated Cardiac Hypertrophy 英文参考文献.docVIP

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Angiotensin-Converting Enzyme 2 Over-Expression in the Central Nervous System Reduces Angiotensin-II-Mediated Cardiac Hypertrophy 英文参考文献.doc

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Angiotensin-Converting Enzyme 2 Over-Expression in the Central Nervous System Reduces Angiotensin-II-Mediated Cardiac Hypertrophy 英文参考文献

Angiotensin-ConvertingEnzyme2Over-Expressionin theCentralNervousSystemReducesAngiotensin-II- MediatedCardiacHypertrophy YumeiFeng1,2,ChetanHans3,ElizabethMcIlwain1,KurtJ.Varner1,EricLazartigues1* 1DepartmentofPharmacologyandExperimentalTherapeuticsandCardiovascularCenterofExcellence,LouisianaStateUniversityHealthSciencesCenter,NewOrleans, Louisiana,UnitedStatesofAmerica,2DepartmentofPhysiology,TulaneUniversity,NewOrleans,Louisiana,UnitedStatesofAmerica,3CenterforCardiovascularand PulmonaryResearch,NationwideChildren’sHospital,Columbus,Ohio,UnitedStatesofAmerica Abstract Angiotensin-converting enzyme type 2 (ACE2) has been shown to be an important member of the renin angiotensin system.Previously,weobservedthatcentralACE2reducesthedevelopmentofhypertensionfollowingchronicangiotensin II(Ang-II)infusioninsyn-hACE2transgenic(SA)mice,inwhichthehumanACE2transgeneisselectivelytargetedtoneurons. TostudythephysiologicalconsequencesofcentralACE2over-expressiononcardiacfunctionandcardiachypertrophy,SA andnon-transgenic(NT)micewereinfusedwithAng-II(600ng/kg/min,sc)for14days,andcardiacfunctionwasassessed byechocardiography.Bloodpressure(BP),hemodynamicparameters,leftventricle(LV)mass/tibialength,relativeventricle wallthickness(2PW/LVD),cardiomyocytediametersandcollagendepositionweresimilar(P.0.05)betweenNTandSAmice duringsalineinfusion.Aftera2-weekinfusion,BPwaselevatedinNTbutnotinSAmice.Althoughejectionfractionand fractional shortening were not altered, Ang-II infusion increased 2PW/LVD compared to saline infusion in NT mice. Interestingly, the 2PW/LVD and LV mass/tibia ratios were significantly lower in SA compared to NT mice at the end of infusion.Moreover,Ang-IIinfusionsignificantlyincreasedarterialcollagendepositionandcardiomyocytesdiameterinNT mice but not in transgenic animals (P,0.05). More importantly, ACE2 over expression significantly reduced the Ang-II- mediated increase in urine norepinephrine levels in SA compared to NT mice. The protective effect of ACE2 appears