Yamagishi H, Kim S, Nishikimi T, Takeuchi K, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
J Mol Cell Cardiol. 1993 Nov;25(11):1369-80. doi: 10.1006/jmcc.1993.1149.
To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynamics and ventricular angiotensin II contents in myocardial-infarcted rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right and left ventricular weight, left ventricular end-diastolic pressure and volume of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor-mediated action of angiotensin II plays a central role in the development of ventricular dilatation. Angiotensin II contents in the right and non-infarcted left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/- S.E.M.) of myocardial-infarcted rats were not different from those of sham-operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/- 3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%, respectively, but did not reduce plasma angiotensin II in myocardial-infarcted rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by 4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was associated with the decrease in ventricular angiotensin II contents. These observations suggest that the cardiac renin-angiotensin system rather than the circulating system may play an important role in ventricular dilatation after myocardial infarction.
为研究心肌梗死后心脏肾素-血管紧张素系统在心室扩张中的作用，我们检测了用血管紧张素转换酶抑制剂地拉普利和选择性血管紧张素II 1型（AT1）受体拮抗剂TCV-116对心肌梗死大鼠进行3周治疗后对血流动力学及心室血管紧张素II含量的影响。TCV-116降低了平均主动脉压，并在与地拉普利相似的程度上阻止了心肌梗死大鼠右心室和左心室重量、左心室舒张末期压力及容积的增加。因此，血管紧张素II的AT1受体介导作用在心室扩张的发展中起核心作用。心肌梗死大鼠右心室和未梗死左心室的血管紧张素II含量（分别为6.0±1.0和5.9±0.7 pg/g组织，均值±标准误）与假手术大鼠无差异。然而，心肌梗死大鼠梗死瘢痕中的血管紧张素II含量（21.7±3.5 pg/g）比假手术大鼠左心室中的高4.2倍。地拉普利使右心室和未梗死左心室以及瘢痕中的血管紧张素II含量分别降低了48%、81%和60%，但未降低心肌梗死大鼠的血浆血管紧张素II。TCV-116也使右心室和未梗死左心室中的血管紧张素II分别降低了57%和56%，同时使血浆血管紧张素II增加了4.3倍。因此，这两种药物对心室扩张的预防作用与心室血管紧张素II含量的降低有关。这些观察结果表明，心脏肾素-血管紧张素系统而非循环系统可能在心肌梗死后的心室扩张中起重要作用。
