TISSUE-SPECIFIC ACTIVATION OF CARDIAC ANGIOTENSIN CONVERTING ENZYME IN EXPERIMENTAL HEART-FAILURE
TISSUE-SPECIFIC ACTIVATION OF CARDIAC ANGIOTENSIN CONVERTING ENZYME IN EXPERIMENTAL HEART-FAILURE
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DOI：
10.1161/01.res.69.2.475
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发表时间：
1991-08-01
影响因子：
20.1
通讯作者：
DZAU, VJ
中科院分区：
文献类型：
--
作者：
HIRSCH, AT;TALSNESS, CE;DZAU, VJ
除了循环中的肾素-血管紧张素系统，最近的数据表明，组织中的肾素-血管紧张素系统的存在，可能是重要的心血管稳态。 然而，循环和组织中的肾素-血管紧张素系统的相对活性以前没有被检查在病理生理状态，如充血性心力衰竭。 本研究观察了冠状动脉结扎致大鼠代偿性心力衰竭时血浆和组织血管紧张素转换酶（ACE）活性的变化。 实验分为三组：1）非手术组（NO，n = 5），2）假手术组（SO，n = 5），3）心衰组（HF，n = 11）。 术后平均85天对大鼠进行研究。 HF动物血浆肾素浓度和血清ACE活性与NO和SO对照动物相比无差异。 心脏ACE活性在NO和SO大鼠的右心室比室间隔大50%。 HF动物的右心室和室间隔ACE活性与NO和SO组相比增加约2倍（p < 0.05）。 与此相反，肺，主动脉和肾脏ACE活性没有改变HF大鼠与对照组相比。 心肌梗死的组织病理学大小与右室ACE活性水平呈正相关（r = 0.75，p ≤ 0.05）。 但没有观察到梗死面积与血清或非心脏组织ACE活性之间的这种关系。 为了证实心脏ACE活性的增加是由于局部合成，检查了来自另外的SO（n = 4）和HF（n = 6）大鼠的右心室心肌，以确定在这种疾病状态下ACE mRNA的相对表达。 通过聚合酶链反应（25个循环）扩增收获的RNA;随后的定量显示ACE mRNA水平增加两倍，这也与梗死面积相关（r = 0.67，p < 0.05）。 这些数据表明，代偿性实验性心力衰竭与心脏ACE活性的组织特异性激活有关，但与血浆或其他组织ACE活性无关。 此外，心脏肾素-血管紧张素系统的这一成分的局部激活似乎与左心室功能障碍的程度直接相关，如梗死面积所示。 增加心脏ACE mRNA水平，ACE活性，和局部合成的血管紧张素II在实验性心力衰竭可能是重要的生理和相关的ACE抑制剂的有益效果。
In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-angiotensin systems have not been examined previously in pathophysiological states, such as congestive heart failure. The present study was performed to examine the status of plasma and tissue angiotensin converting enzyme (ACE) activities in compensated experimental heart failure induced by coronary artery ligation in the rat. Three groups of male Sprague-Dawley rats were examined: 1) nonoperated rats (NO, n = 5), 2) sham-operated rats (SO, n = 5), and 3) heart failure rats (HF, n = 11). Rats were studied an average of 85 days postoperatively. In HF animals, plasma renin concentration and serum ACE activities were not different compared with NO and SO control animals. Cardiac ACE activity was 50% greater in the right ventricle than the interventricular septum in NO and SO rats. Both right ventricular and interventricular septal ACE activity increased approximately twofold in HF animals as compared with NO and SO groups (p < 0.05). In contrast, pulmonary, aortic, and renal ACE activities were not altered in HF rats compared with control animals. A positive correlation existed between the histopathological size of myocardial infarction and the level of right ventricular ACE activity (r = 0.75, p less-than-or-equal-to 0.05). Such a relation between infarct size and either serum or noncardiac tissue ACE activities was not observed. To confirm that increased cardiac ACE activity was due to local synthesis, right ventricular myocardium from additional SO (n = 4) and HF (n = 6) rats was examined to determine the relative expression of ACE mRNA in this disease state. Harvested RNA was amplified by polymerase chain reaction (25 cycles); subsequent quantitation demonstrated a twofold increase in ACE mRNA level that also correlated with infarct size (r = 0.67, p < 0.05). These data demonstrate that compensated experimental heart failure is associated with tissue-specific activation of cardiac ACE activity, but not plasma or other tissue ACE activities. Additionally, the local activation of this component of the cardiac renin-angiotensin system appears to be directly associated with the magnitude of left ventricular dysfunction as suggested by the infarct size. Increased cardiac ACE mRNA level, ACE activity, and local synthesis of angiotensin II in experimental heart failure may be physiologically important and pertinent to the beneficial effects of ACE inhibition.