【摘要】 目的探讨血管紧张素转换酶(ACE)和血管紧张素原(AGT)基因多态及ACE和血管紧张素Ⅱ1型受体(AT1)mRNA表达与抗高血压药物降压效应间的关系。方法随机、单盲设计,入选90名原发性高血压患者随机分为3组,分别给予氯沙坦(Losartam)、赖诺普利(Lisinoprtl)及尼索地平(Nisodrpine),并测定患者ACE基因插入(I)/缺失(D)、AGT基因M235T多态及ACE、AT1 基因mRNA表达。结果①AT1 mRNA表达基础值在AGT基因MT及TT基因型明显高于MM型,而MT与TT型间无差异;②三种抗高血压药物在显著降低血压同时,也明显降低AT1 mRNA表达;③氯沙坦及赖诺普利降低ACEmRNA表达,且与舒张期血压(DBP)差值呈正相关,而尼索地平反使ACEmRNA表达升高,与DBP差值负相关。结论依据AT1 mRNA表达基础水平增高且同时为AGTT等位基因者或ACEmRNA表达基础高水平者均可优选作用于肾素系(RAS)的ACEI或AT1拮抗剂;而ACEmRNA表达基础低水平者则选择钙通道拮抗剂。更多还原

【Abstract】 Objective To investigatetherelationof renin-angiotensinsystem(RAS)genepolymorphismsandexpressionswith theclinicalefficacyof antihypertensivedrugs.Methods Thisrandomized,single-blindstudyconsisted of90patientswith essentialhypertension,who weredividedintolosartan,lisinoprilandnisodipinegroupswithcorrespondingmedicationsas indicated.Thegenotypesof angiotensin-convertingenzyme(ACE)insertion/deletion,angiotensinogen(AGT)M235T polymorphismandexpressionsof ACEandAT 1 receptorgeneswereexaminedindividually.Results Thebasallevelof mRNA expressionof AT 1 receptorwas lowerin patientswithMM genotypeof AGT genethanthosein patientswithMT and TT genotypes,but betweenthelattertwo,no significantdifferenceswerefound. The threeantihypertensivedrugs,when significantlyloweringthebloodpressure,reducedAT 1 receptormRNAexpressionconcurrently. Losartanandlisinoprilboth decreasedACEmRNAexpressionlevelsthatwerepositivelycorrelatedwith thedifferenceof thediastolicbloodpressure,whereasnisodipineelevatedACEmRNAexpression,showinginversecorrelationto the differenceof thediastolicblood pressure.Conclusion Forpatientswithhypertensionwho haveelevatedbasallevelsof AT 1 mRNAexpressionandAGTT alleleor whoretainhighbasalexpressionlevelsof ACEmRNA,AT 1 antagonistsandACEinhibitors thatexecutetheiraction throughRASarepreferentiallyselected,andincasesof lowbasallevelsof ACEmRNA,calciumantagonistsarepreferred.更多还原