高血压左心室肥厚与血管紧张素Ⅱ受体的关系

The Relationship of Left Ventricular Hypertrophy and Angiotensin Ⅱ Receptor in Spontaneously Hypertensive Rats

目的 :探讨自发性高血压大鼠 (SHR)左心室肥厚和血管紧张素 (Ang )受体的关系。 方法 :雄性 SHR自 10周龄始 ,给予依那普利 [enalapril2 0 mg/ (kg· d) ],氯沙坦 [losartan2 5 mg/ (kg· d) ],或二者半剂量合用 [依那普利 10 mg/ (kg· d) ,氯沙坦 12 .5 mg/ (kg· d) ]6周 ,并以鼠龄、性别、数量相同的未治疗 SHR和WKY作对照。测量收缩压、左心室重量 (L VM)及左心室重量指数 (L VMI)。采用 RT- PCR方法检测心肌组织内 AT1和AT2受体基因信使核糖核酸 (m RNA)表达 ,用放射配基结合法测定心肌组织内 Ang 受体密度。 结果 :SHR对照组的收缩压、L VM和 L VMI均显著高于 WKY对照组 (P<0 .0 0 1) ,SHR各治疗组上述指标显著低于其 WKY对照组 (收缩压 ,P<0 .0 0 1;L VM和 L VMI,P<0 .0 1) ,依那普利和氯沙坦之间无显著差别 ,二者合用比单用对降低 L VMI更有效 (P<0 .0 5 )。 SHR对照组 AT1受体 m RNA表达和 Ang 受体密度显著高于 WKY对照组 (P<0 .0 0 1) ,SHR+氯沙坦组较 SHR对照组显著降低 (P<0 .0 0 1) ,而 AT2受体无改变。 SHR+依那普利组 AT1、AT2受体m RNA表达及 Ang 受体密度均无改变。 结论 :高血压左心室肥厚时出现 Ang 受体主要是 AT1受体上调 ,这可能与血压和心脏肥厚有关。

Objective:To investigate the relationship between left ventricular hypertrophy and angiotensin Ⅱ(AngⅡ)receptor in spontaneously hypertensive rats (SHR). Methods:We administered AngⅡreceptor type 1(AT1) antagonist [losartan 25 mg/(kg·d)],angiotensin converting enzyme (ACE) inhibitor[enalapril 20 mg/(kg·d)],or their combination at half doses [losartan 12.5 mg/(kg·d),enalapril 10 mg/(kg·d)] to SHR from 10 to 16 weeks of age.Male,age matched untreated SHR (SHRc) and Wistar Kyoto (WKY) rats served as controls.Systolic blood pressure (SBP),left ventricular mass (LVM) and left ventricular mass index (LVMI) were determined.AT1 and AT2 receptor mRNA expressions were assessed by reverse transcription polymerase chain reaction(RT PCR).AngⅡ receptor densities were determined using binding assay in ventricular tissue. Results:Compared with WKY rats,the SBP,LVM and LVMI were significantly increased in SHRc ( p< 0.001),which were significantly reduced in treated SHR than in SHRc (SBP, p< 0.001,LVM and LVMI, p< 0.01).The combination of enalapril with losartan induced greater reduction in LVMI ( p< 0.05).The AT1 receptor mRNA expression and AngⅡ receptor density were significantly increased in SHRc than that in WKY rats ( p< 0.001).In losartan treated group,AT1 mRNA expression and AngⅡ densities were reduced ( p< 0.001),while AT2 receptor expression was not altered.In enalapril treated group,there were no changes in AT1,AT2 receptor mRNA expression and AngⅡ receptor densities. Conclusions:In left ventricular hypertrophy,AngⅡ receptor,mainly AT1 receptor,is upregulated,and which may be involved in blood pressure and cardiac hypertrophy.Losartan and enalapril can equally reduce blood pressure and reverse left ventricular hypertrophy,but the mechanisms of their action are different.