小剂量联合应用缬沙坦和雷米普利对原发性高血压大鼠体内NO水平及心肌重塑的影响  

Effects of Low Dose of Valsartan Plus Ramipril on NO Levels and Cardiac Remodeling in SHRs

作　　者：郑永红[1] 白玉茹[1] 胡锡衷[1] 郑伟[2] 

机构地区：[1]福建省立医院心内科,福建省福州市350001 [2]福建医科大学病理教研室

出　　处：《中国全科医学》2007年第3期211-214,共4页Chinese General Practice

摘　　要：目的 探讨小剂量联合应用血管紧张素Ⅱ1型受体（AT1R）拮抗剂（ARB）缬沙坦和血管紧张素转化酶抑制剂（ACEI）雷米普利原发性高血压大鼠（SHR）体内一氧化氮（NO）的改变和对高血压心肌重塑的影响。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组分剐用缬沙坦（30mg·k^-1·d^-1），雷米普利（1mg·kg^-1·d^-1）和缬沙坦（15mg·kg^-1·d^-1）＋雷米普利（0，5mg·kg^-1·d^-1）灌胃。3个月后，分别测定血压、心重与体重比值、血浆血管紧张素Ⅱ（AngⅡ）水平，血清NO值及心肌、脑和肾组织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。用反转录聚合酶链式反应（RT—PCR）方法测定各组大鼠左室心肌ACEmRNA、AT1RmRNA和AT2RmRNA表达情况。结果 发现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大鼠心肌AT1RmRNA和ACEmRNA的表达；明显提升了AT2RmRNA与AT1RmRNA比值；同时增高了局部心肌、脑和肾组织NO的含量。结论 小剂量联合应用缬沙坦和雷米普利提升重要脏器的NO值并抑制高血压心肌重塑。Objective To study the influence of combined low dose of angiotensin Ⅱ type 1 receptor antagonist Valsartan with angiotensin -converting enzyme inhibitor Ramipril on the NO levels and the hypertensive cardiac remodeling in SHRs. Methods Seven or eight weeks old male SHRs （ n = 24） and WKYs （ n = 8） were obtained. SHRs were divided into four groups （n =6 in each） , Valsartan （30 mg· kg^-1·d^-1）, Ramipril （1 mg · kg^-1· d^-1）, or Valsartan （15 mg· kg^-1· d^-1） plus Ramipril （0.5 mg· kg^-1· d^-1 ） were administered respectively to three groups by garage. After three months, systolic blood pressure, cardiac weight to body weight ratio and Angiotensin Ⅱ levels in plasma were measured. NO levels in serum, heart, encephalon and kidney were measured too. By means of image analysis, the degrees of myocardial interstitial fibrosis was assessed. At 1 ast, the levels of ACEmRNA, AT1RmRNA and AT2RmRNA expression were detected in the left ventricular myocardium of rats in each group by using RT - PCR method. Results Combined half dose of Valsartan and Ramipril can more completely reduce the expression of AT1RmRNA and ACEmRNA in myocardium than Valsartan or Ramipril alone. And it can clearly increase the rate of AT2RmRNA to AT1RmRNA. At the same time it could also especially upgrade NO content in myocardium, encephalon and kidney. Conclusion Combined low dose of Valsartan and Ramipril increases NO levels in essential organs and inhibits remodeling of hypertensive myocardium.

关 键 词：缬沙坦 雷米普利 联合应用 一氧化氮 心肌重塑 

分 类 号：R972[医药卫生—药品]