人及动物心脏中血管紧张素转换酶（ACE）和糜酶生成血管紧张素II的过程：方法及物种考量

Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations.

作者信息

Balcells E, Meng Q C, Johnson W H, Oparil S, Dell'Italia L J

机构信息

Birmingham Veteran Affairs Medical Center, Department of Medicine, University of Alabama, 35294, USA.

出版信息

Am J Physiol. 1997 Oct;273(4):H1769-74. doi: 10.1152/ajpheart.1997.273.4.H1769.

DOI:10.1152/ajpheart.1997.273.4.H1769

PMID:9362242

Abstract

The current study examined the contributions of angiotensin-converting enzyme (ACE) vs. chymase to angiotensin II (ANG II) generation in membrane preparations from left ventricles of humans, dogs, rabbits, and rats and from total heart of mice. ACE and chymase activity were measured in membrane preparations extracted with low or high detergent (LD and HD, respectively) concentrations. We hypothesized that ACE, which is membrane bound in vivo, would be preferentially localized to the HD preparation, whereas chymase, which is localized to the cytoplasm and cardiac interstitium, would be localized to the LD preparation. In human heart, ACE activity was 16-fold higher in the HD than in the LD preparation, whereas chymase activity was 15-fold higher in the LD than in the HD preparation. Total ANG II formation was greater in human heart [15.8 +/- 3.4 (SE) micromol ANG II x g(-1) x min(-1)] than in dog, rat, rabbit, and mouse hearts (3.90 +/- 0.35, 0.41 +/- 0.02, 0.61 +/- 0.07, and 1.16 +/- 0.08 micromol ANG II x g(-1) x min(-1), respectively, P < 0.05, by analysis of variance). ANG II formation from ACE was higher in mouse heart (1.09 +/- 0.05 micromol ANG II x g(-1) x min(-1), p < 0.001) than in rabbit, human, dog, and rat hearts (0.55 +/- 0.06, 0.34 +/- 0.01, 0.32 +/- 0.06, and 0.31 +/- 0.02 micromol ANG II x g(-1) x min(-1), respectively). In contrast, chymase activity was higher in human heart (15.3 +/- 3.4 micromol ANG II x g(-1) x min(-1)) than in dog, rat, rabbit, and mouse hearts (3.59 +/- 0.29, 0.10 +/- 0.01, 0.06 +/- 0.01, and 0.07 +/- 0.01 micromol ANG II x g(-1) x min(-1), respectively). Our results demonstrate important species differences in the pathways of intracardiac ANG II generation. Chymase predominated over ACE activity in human heart, accounting for extremely high total ANG II formation in human heart compared with dog, rat, rabbit, and mouse hearts.

摘要

本研究检测了在人、犬、兔、大鼠左心室及小鼠全心的膜制剂中，血管紧张素转换酶（ACE）与糜酶对血管紧张素II（ANG II）生成的作用。用低或高浓度去污剂（分别为LD和HD）提取膜制剂并测定ACE和糜酶活性。我们推测，在体内与膜结合的ACE将优先定位于HD制剂，而定位于细胞质和心脏间质的糜酶将定位于LD制剂。在人心脏中，HD制剂中的ACE活性比LD制剂高16倍，而LD制剂中的糜酶活性比HD制剂高15倍。人心脏中ANG II的总生成量[15.8±3.4（SE）μmol ANG II×g⁻¹×min⁻¹]高于犬、大鼠、兔和小鼠心脏（分别为3.90±0.35、0.41±0.02、0.61±0.07和1.16±0.08μmol ANG II×g⁻¹×min⁻¹，方差分析，P<0.05）。小鼠心脏中由ACE生成的ANG II高于兔、人、犬和大鼠心脏（分别为1.09±0.05μmol ANG II×g⁻¹×min⁻¹，p<0.001；0.55±0.06、0.34±0.01、0.32±0.06和0.31±0.02μmol ANG II×g⁻¹×min⁻¹）。相反，人心脏中的糜酶活性（15.3±3.4μmol ANG II×g⁻¹×min⁻¹）高于犬、大鼠、兔和小鼠心脏（分别为3.59±0.29、0.10±0.01、0.06±0.01和0.07±0.01μmol ANG II×g⁻¹×min⁻¹）。我们的结果表明，心脏内ANG II生成途径存在重要的物种差异。在人心脏中，糜酶的活性高于ACE，这导致人心脏中ANG II的总生成量与犬、大鼠、兔和小鼠心脏相比极高。