【摘要】 目的探讨小剂量联合应用血管紧张素Ⅱ1型受体阻滞剂(ARB)缬沙坦和血管紧张素转化酶抑制剂(ACEI)雷米普利对自发性高血压大鼠(SHR)体内血管紧张素Ⅱ1型受体(AT1R)和2型受体(AT2R)基因表达的影响及该方法治疗高血压的可行性。方法7～8周龄雄性SHR大鼠24只,WKY大鼠8只。SHR大鼠分成4组,每组6只。其中3组分别用缬沙坦30mg/(kg.d),雷米普利1mg/(kg.d)和缬沙坦15mg/(kg.d)+雷米普利0.5mg/(kg.d)灌胃。3月后,分别测定血压、心质量与体质量比值、血浆血管紧张素Ⅱ(AngⅡ)值,血清一氧化氮(NO)值及心肌组织NO值。应用心肌胶原纤维特殊染色法及图像分析评估大鼠心肌纤维化程度。用RT-PCR方法测定各组大鼠左室心肌,主动脉及脑组织ACEmRNA、AT1RmRNA和AT2RmRNA表达情况。结果联合应用半量的缬沙坦和雷米普利比单用组更全面抑制了SHR心肌、主动脉和脑组织中AT1RmRNA和ACEmRNA的表达(AT1RmRNA:P<0.01vs雷米普利组;ACEmRNA:P<0.01vs缬沙坦组)。联合组明显提升了AT2RmRNA与AT1RmRNA比值(约为SHR组、WKY组或雷米普利组3～4倍),增高了局部心肌组织NO的含量[联合组(7.2±1.2)vsSHR组(4.7±1.2),P<0.05]。结论小剂量联合应用缬沙坦和雷米普利比单用组在高血压治疗方面获益更大。更多还原

【Abstract】 Objective To study the efficacy of low dose of combined angiotensin Ⅱ type 1 receptor blockade(ARB)valsartan with angiotensin-converting enzyme inhibitor(ACEI)ramipril on the expression of the gene of angiotensin Ⅱ type 1 receptor(AT1R)and type 2 receptor(AT2R)in cardiovascular vessels and brain in SHR.Methods SHRs 7-8 weeks old were received valsartan 30 mg/(kg·d),or ramipril 1 mg/(kg·d),or valsartan 15 mg/(kg·d)combined with ramipril 0.5 mg/(kg·d)by gavage for three months.SBP,LV/BW ratio,plasma angiotensin Ⅱ,plasma and myocardial NO levels were determined.The severity of myocardial interstitial fibrosis was assessed by image analysis.ACE mRNA,AT1R mRNA and AT2R mRNA expression were detected in the LV myocardium,aorta and brain by the RT-PCR.Results Combined low dose of valsartan and ramipril was shown to reduce more significantly the expression of AT1R mRNA and ACE mRNA in myocardium,aorta and brain than valsartan or ramipril monotherapy(AT1R mRNA:P<0.01 vs ramipril;ACE mRNA:P<0.01 vs valsartan),which was associated with upregulated of AT2R/AT1R mRNA ratio by 3-4 folds as compared with that in SHR,WKY or ramipril treatment alone group.Conclusion Combination of low dose of valsartan and ramipril therapy was more effective in reduction of AT1R mRNA and increases in AT2R mRNA in aorta,myocardium,and brain than valsartan or ramipril alone in SHR.更多还原