Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation
Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation
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DOI：
10.1152/ajpheart.1995.269.6.h2065
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发表时间：
1995-12-01
影响因子：
4.8
通讯作者：
Elton, TS
中科院分区：
文献类型：
--
作者：
DellItalia, LJ;Meng, QC;Elton, TS
目前的研究旨在验证这样一种假设，即在狗经皮脊索破裂引起的二尖瓣反流慢性低压容积超载的情况下，心内血管紧张素转换酶（ACE）活性、乳糜样活性和血管紧张素（ANG）肽水平升高，并与壁应力估计呈正相关。慢性二尖瓣反流（MR）导致左室（LV）舒张末期容积增加[59 +/- 11 （SD）至103 +/- 32 mi， P < 0.001]，左室质量（96 +/- 17至114 +/- 23 g， P < 0.001），左室质量与舒张末期容积比降低（1.64 +/- 0.22至1.16 +/- 0.23 g/ml, P < 0.001）。心脏组织提取物的体外研究表明，在5个正常心脏（83.5 +/- 7.5 vs. 6.04 +/- 5.2%）和7个MR心脏（86 +/- 3.9 vs. 2.6 +/- 1.7%）中，大部分ANG ii形成活性来自于乳糜样活性，而不是ACE活性。ACE活性（1.22 +/- 0.22 vs. 3.55 +/- 0.62 mU/g, P < 0.05）和乳糜样活性（9.42 +/- 4.64 vs. 20.60 +/- 8.41 nmol）。g(1)。min(-1), P < 0.05)与正常心脏相比增高。ACE活性与左室质量容积比（r = -0.93, P < 0.001）和左室舒张壁应力（r = 0.71, P < 0.05）相关；然而，乳糜样活性与任何血流动力学参数无关。MR心脏左心室中壁ANG II水平明显高于正常对照组（85 +/- 39 vs. 27 +/- 16 pg/g, P < 0.01）。我们的研究结果表明，左心室舒张壁应力与ACE活性增加呈正相关，ANG II储存增加，表明机械壁应力激活了心内ACE。尽管在正常和MR狗的心脏提取物中，乳糜酶在体外形成了大多数ANG II，但这种酶在体内的意义尚不清楚。
The current study was designed to test the hypothesis that intracardiac angiotensin-converting enzyme (ACE) activity, chymase-like activity, and angiotensin (ANG) peptide levels are increased and are positively related to wall stress estimates in response to the chronic low pressure volume overload of mitral regurgitation produced by percutaneous chordal rupture in the dog. Chronic mitral regurgitation (MR) resulted in an increase in left ventricular (LV) end-diastolic volume [59 +/- 11 (SD) to 103 +/- 32 mi, P < 0.001], LV mass (96 +/- 17 to 114 +/- 23 g, P < 0.001), and a decrease in the LV mass-to-end-diastolic volume ratio (1.64 +/- 0.22 to 1.16 +/- 0.23 g/ml, P < 0.001) measured by magnetic resonance imaging. In vitro studies of heart tissue extracts demonstrated that the majority of ANG II-forming activity was from chymase-like activity rather than from ACE activity in five normal (83.5 +/- 7.5 vs. 6.04 +/- 5.2%) and seven MR hearts (86 +/- 3.9 vs. 2.6 +/- 1.7%). ACE activity (1.22 +/- 0.22 vs. 3.55 +/- 0.62 mU/g, P < 0.05) and chymase-like activity (9.42 +/- 4.64 vs. 20.60 +/- 8.41 nmol . g(-1). min(-1), P < 0.05) were increased in MR compared with normal hearts. ACE activity correlated with the LV mass-to-volume ratio (r = -0.93, P < 0.001) and LV diastolic wall stress (r = 0.71, P < 0.05); however, chymase-like activity did not correlate with any hemodynamic parameter. ANG II levels were significantly higher in the midwall of the left ventricle in MR hearts than in normal controls (85 +/- 39 vs. 27 +/- 16 pg/g, P < 0.01). Our results demonstrate a positive correlation between LV dia stolic wall stress and increased ACE activity with increased ANG II stores, suggesting that mechanical wall stress activated intracardiac ACE. Although chymase accounted for most ANG II formation in vitro in extracts of both normal and MR dog hearts, the significance of this enzyme in vivo remains unclear.