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Birmingham Veteran Affairs Medical Center and Division of Cardiovascular Disease, Department of Medicine, Vascular Biology and Hypertension Program, and Division of Pediatric Cardiology, Department of Pediatrics, University of Alabama, Birmingham, Alabama 35294
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) µmol ANG
II · g
1 · min1]
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 µmol ANG
II · g1 · min1,
respectively, P < 0.05, by
analysis of variance). ANG II formation from ACE was higher in mouse
heart (1.09 ± 0.05 µmol ANG
II · g1 · min1,
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 µmol ANG
II · g1 · min1,
respectively). In contrast, chymase activity was higher in human heart
(15.3 ± 3.4 µmol ANG
II · g1 · min1)
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 µmol ANG
II · g1 · min1,
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.
angiotensin-converting enzyme; detergent renin-angiotensin system
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