氯沙坦对慢性心力衰竭大鼠循环与心脏组织去甲肾上腺素和RAAS的影响及心功能的保护作用

目的研究AT1受体拮抗剂氯沙坦（Los）对循环和心脏局部组织去甲肾上腺素（NE）和肾素-血管紧张素-醛固酮系统（RAAS）的影响以及心功能的保护作用。方法Sprague—Dawley（SD）大鼠40只，随机分为4组，即腹主动脉缩窄（COA）＋Vehiele组；COA＋Los组、假手术（Sham）＋Vehicle组、Sham＋Los组。Los干预8周后采用超声心动图和心室插管法评估各组大鼠的心功能，计算左、右心室质量指数（LVMI、RVMI），采用酶联免疫吸附法（ELISA）和放射免疫法（RIA）测定血浆和心肌组织NE、血管紧张素Ⅱ（AngⅡ）和醛固酮（ALD）含量。结果COA＋Vehicle组循环和心肌组织中AngⅡ和ALD含量显著高于Sham组（P〈0．05），循环NE水平增高而心肌组织NE含量降低；COA＋LOS组循环AngⅡ水平增高，NE和ALD水平显著低于COA＋Vehiele组（P〈0．05）；心肌组织NE含量增高，而AngⅡ和ALD含量显著低于COA＋Vehicle组（P〈0．05）。心肌AngⅡ和ALD含量均与LVEDP呈显著性正相关（r1=0．8251，r2=0．8018，P〈0．01），其相关性强于循环AngⅡ和ALD。结论心脏局部组织RAAS而非循环RAAS在慢性压力超负荷致心力衰竭中起重要作用，Los防止心肌肥厚和延缓心功能恶化的重要机制之一是阻断心脏组织RAAS，抑制心肌组织局部AngⅡ生成和机体交感神经系统激活。

Effects of Losartan on Circulating and Local Norepinephrine and Renin - angiotensin - aldosterone System in Rats with Chronic Heart Failure

Objective To investigate the effects of Losartan （Los） on circulating and local norepinepbrine（NE）and renin-angiotension- aldosterone system（RAAS） in chronic heart failure（CHF） rats induced by banding abdominal aorta. Methods Forty Sprague - Dawley rats were randomly divided into four groups：Coarctation of abdominal aorta（COA）＋Vehicle group, COA＋Los group, sham - operated （ Sham ＋ Vehicle ） group and Sham＋ Los group. After 8 weeks , the cardiac function were evaluated by ultrasound cardiograph and Powertab system through the pressure transducers. The ventricular mass index（VMI）was observed. Circulating and ventricular NE, angiotensin Ⅱ （Ang Ⅱ ） and aldosterone （ALD） were measured by ELISA and RIA respectively. Results Levels of circulating and local Ang Ⅱ and ALD in COA＋Vehicle group were significantly highter than those in Sham group（P〈0.05）, while levels of circulating NE was increased and levels of circulating NE was decreased. Levels circulating NE and ALD in COA＋Los group were significantly lower than those in.：COA＋Vehicle group（P〈0.05）,while levels of circulating Ang Ⅱ was increased. Cardiac Ang Ⅱ and ALD were significantly lower than those in COA＋Vehicle group（P〈0.05） ,while levels of NE was increased. Left ventricular end - diastolic pressure （ LVEDP ） was obviously positive correlated with both myocardial Ang Ⅱ and ALD （ r1 = 0 . 8251 , r2 = 0. 801 8,P〈0.05） ,and the correlation was stronger than those in circulating Ang Ⅱ and ALD. Conclusion The Results suggested that cardiac RAAS might play an important role in the heart failure during chronic pressure over - loading. A mechanism of preventing cardiac hypertrophy and delaying cardiac function deterioration by losartan was due to blocking cardiac RAAS,inhibiting the produc- tion of myocardial Ang Ⅱ and the activity of sympathetic nervous system.