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1、?reduceCHF-associatedmorbidityandmortalityrates?mayhaveamorefavorableeffectonqualityoflife第二十三章肾素-血管紧张素系统药理（Renin–angiotensinsystem,RAS）肾素－血管紧张素系统药理一、肾素－血管紧张素系统及意义（了解）二、肾素－血管紧张素系统阻断药1、血管紧张素转化酶抑制剂（ACEI）①共性（掌握）②常用的ACEI（熟悉）2、AT1-R阻断剂①作用特点及应用（掌握）②常用药（熟悉）血管紧张素原血管紧张素Ⅰ血管紧张素Ⅱ肾素－血管紧张素系统血
2、管紧张素转换酶（ACE）AT1受体AT2受体1.血管收缩→外周阻力↑2.Ald释放→水钠潴留3.促生长增殖→心血管重构1.与胎儿发育有关2.激活NOS3.部分对抗AT1的促增殖作用肾素ComponentsoftheRASAngII,themostactiveangiotensinpeptide,isderivedfromangiotensinogenintwoproteolyticsteps.renin,anenzymereleasedfromthekidneys,cleavesthedecapeptideAngIfromtheaminoterminu
3、sofangiotensinogen(reninsubstrate).ACE,removesthecarboxy-terminaldipeptideofAngItoproducetheoctapeptideAngII.AT1andAT2,AngIIactsbybindingtotwoheptahelicalGPCRs,TheunderstandingoftheRAShasexpandedinrecentyears.ThecurrentviewoftheRASalsoincludesalocal(tissue)RAS,alternativepathway
4、sforAngIIsynthesis(ACEindependent),formationofotherbiologicallyactiveangiotensinpeptides(AngIII,AngIV,Ang[1–7),additionalangiotensinbindingreceptors(angiotensinsubtypes1,2,and4[AT1,AT2,AT4];Mas)thatparticipateincellgrowthdifferentiation,hypertrophy,inflammation,fibrosis,andapopt
5、osis.局部组织RAS（localtissueRAS）部位：心肌、血管、肝、肾、血管、粘膜等AngIAngII自分泌、旁分泌等方式发挥作用。心血管组织中的RAS在高血压、心血管重构、动脉粥样硬化等发生发展过程中起重要作用。糜酶、ACEFormationofangiotensinsI-IVfromtheN-terminaloftheprecursorproteinangiotensinogenAngiotensinPeptidesAngI(1-10)AngII(1-8)AT1-RandAT2-RAngIII(2-8)AT1-R/?AngIV(3-8)A
6、T4-R(IRAP)/?Ang(1-7)Mas-RCurrentviewoftherenin–angiotensinsystemcascadeAbbreviations:ACE,angiotensin-convertingenzyme;Ang,angiotensin;AMP,aminopeptidase;AT1,AngIItype1receptor;AT2,AngIItype2receptor;Mas,Ang(1–7)receptorMas;D-Amp,dipeptidyl-...SantosRASetal.ExpPhysiol2008;93:519-
7、527SchematicrepresentationoftheenzymaticpathwaysinvolvedinthegenerationofangiotensinpeptidesAngiotensinReceptorsMostoftheknownbiologicaleffectsofAngIIaremediatedbytheAT1-R.associatedwithhypertension,hypertrophiccardiomyopathy,andcoronaryarteryvasoconstriction.Functionalrolesfort
8、heAT2-Rarelesswelldefined,buttheymaycounterbala
