Pfeifer M, Bruckschlegel G, Holmer S R, Paul M, Riegger A J, Schunkert H
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität, Regensburg, Germany.
Cardiovasc Res. 1998 Apr;38(1):125-32. doi: 10.1016/s0008-6363(97)00298-8.
Numerous studies support the concept that cardiac angiotensin-converting enzyme (ACE) is involved in the pathophysiology of left ventricular hypertrophy. However, the pulmonary vasculature is considered to be the most prominent site of ACE expression. We thus examined the tissue specificity of ACE regulation in rats with severe cardiac pressure overload hypertrophy in transition to cardiac failure with secondary pulmonary hypertension.
Rats were studied 12 weeks after banding of the ascending aorta (LVH, n = 20) that resulted in a 1.7-fold increase in left ventricular (LV) to body weight ratio. In addition, as compared to sham-operated rats (n = 20), we observed in LVH rats a 1.6-fold increase in right ventricular (RV) to body weight ratio, the development of pulmonary hypertension, and elevated plasma renin activities. Moreover, ACE mRNA and activity levels were more than 2-fold higher in both hypertrophied ventricles (P < 0.01, each). In contrast, pulmonary ACE mRNA and activity levels were markedly decreased in animals with LVH (more than 30%, respectively, P < 0.05 vs. sham), Interestingly, LV and RV ACE activity, as well as systolic pulmonary artery pressure and plasma renin activity, were all inversely related to pulmonary ACE activity. In order to differentiate the potential role of elevated renin in the down-regulation of pulmonary ACE, additional rats (n = 12) were treated with furosemide that resulted in a 8-fold rise in plasma renin activity, but only in a marginal decrease of pulmonary ACE mRNA levels and activity (-10% vs. sham (n = 8), P-value n.s.).
The data indicate tissue specific reciprocal regulation of pulmonary and cardiac ACE in rats with cardiac pressure overload hypertrophy and pulmonary hypertension, a phenomenon that may potentially result in a partial shift of angiotensin II formation from the pulmonary to the cardiac circulation.
众多研究支持心脏血管紧张素转换酶（ACE）参与左心室肥厚病理生理学的概念。然而，肺血管系统被认为是ACE表达最显著的部位。因此，我们研究了严重心脏压力超负荷肥大向继发于肺动脉高压的心力衰竭转变过程中大鼠ACE调节的组织特异性。
在升主动脉缩窄12周后对大鼠进行研究（左心室肥厚，n = 20），这导致左心室（LV）与体重比增加1.7倍。此外，与假手术大鼠（n = 20）相比，我们观察到左心室肥厚大鼠右心室（RV）与体重比增加1.6倍，出现肺动脉高压，且血浆肾素活性升高。此外，肥厚的两个心室中ACE mRNA和活性水平均高出2倍以上（均P < 0.01）。相比之下，左心室肥厚动物的肺ACE mRNA和活性水平显著降低（分别超过30%，与假手术组相比P < 0.05）。有趣的是，左心室和右心室ACE活性以及收缩期肺动脉压和血浆肾素活性均与肺ACE活性呈负相关。为了区分肾素升高在肺ACE下调中的潜在作用，另外对大鼠（n = 12）用速尿治疗，这导致血浆肾素活性升高8倍，但仅使肺ACE mRNA水平和活性略有下降（与假手术组（n = 8）相比降低10%，P值无统计学意义）。
数据表明，在心脏压力超负荷肥大和肺动脉高压的大鼠中，肺和心脏ACE存在组织特异性的相互调节，这一现象可能会导致血管紧张素II的形成从肺循环部分转移至心脏循环。
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