局部生成的血管紧张素II和缓激肽在减小犬心肌梗死面积中的作用

Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs.

作者信息

Noda K, Sasaguri M, Ideishi M, Ikeda M, Arakawa K

机构信息

Department of Internal Medicine, Fukuoka University School of Medicine, Japan.

出版信息

Cardiovasc Res. 1993 Feb;27(2):334-40. doi: 10.1093/cvr/27.2.334.

DOI:10.1093/cvr/27.2.334

PMID:8472285

Abstract

OBJECTIVE

The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size.

METHODS

Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique.

RESULTS

Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group.

CONCLUSIONS

Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation.

摘要

目的

研究血管紧张素II和缓激肽的局部生成在减小心肌梗死面积中的作用。

方法

使用双侧肾切除的雄性杂种犬。比较三种血管紧张素II生成酶抑制剂——卡托普利（一种血管紧张素转换酶抑制剂）、那法莫司他（一种丝氨酸蛋白酶抑制剂）和抑肽酶（一种半胱氨酸蛋白酶抑制剂）预处理对左前降支冠状动脉闭塞的影响。监测血流动力学变量，并从前室间静脉和主动脉采集血液。通过放射免疫分析法测定血管紧张素I、血管紧张素II和缓激肽。闭塞90分钟后，采用宏观酶技术测定梗死面积。

结果

前室间静脉中血管紧张素II的释放量从冠状动脉闭塞前的0.03（标准误1.19）pg·min⁻¹增加至4.64（1.37）pg·min⁻¹（n = 14，p < 0.05），而血管紧张素I的释放量和血浆肾素活性保持不变。那法莫司他和抑肽酶可抑制血管紧张素II释放的增加，但卡托普利不能。缓激肽的释放量在闭塞后30分钟从-3.18（2.72）（冠状动脉闭塞前）增加至34.7（12.3）pg·min⁻¹（n = 14，p < 0.05）。卡托普利可增强这种增加，从闭塞前的4.10（2.86）增加至闭塞后5分钟的97.8（39.6）pg·min⁻¹（n = 12，p < 0.05），但那法莫司他或抑肽酶不能。卡托普利组的梗死面积小于对照组（p < 0.05）。