Vol. 278, Issue 6, L1280-L1288, June 2000
Reduced lung endothelial angiotensin-converting
enzyme activity in Watanabe hyperlipidemic rabbits in
vivo
Stylianos E.
Orfanos1,
James B.
Parkerson1,2,
Xilin
Chen2,
Eugene L.
Fisher3,
Constantinos
Glynos1,
Andreas
Papapetropoulos1,2,
Ross G.
Gerrity4, and
John D.
Catravas1,2
2 Vascular Biology Center,
1 Department of Pharmacology and Toxicology,
3 Department of Pediatrics, and
4 Department of Pathology, Medical College of
Georgia, Augusta, Georgia 30912
We investigated
pulmonary endothelial function in vivo in 12- to 18-mo-old male
Watanabe heritable hyperlipidemic (WHHL; n = 7) and age- and
sex-matched New Zealand White (n = 8) rabbits. The animals were
anesthetized and artificially ventilated, and the chest was opened and
put in total heart bypass. The single-pass transpulmonary utilizations
of the angiotensin-converting enzyme (ACE) substrate
[3H]benzoyl-Phe-Ala-Pro (BPAP) and the
5'-nucleotidase (NCT) substrate [14C]AMP were estimated, and the
first-order reaction parameter
Amax/Km, where
Amax is the product of enzyme mass and the catalytic
rate constant and Km is the Michaelis-Menten
constant, was calculated. BPAP transpulmonary utilization and
Amax/Km were reduced in WHHL (1.69 ± 0.16 vs. 2.9 ± 0.44 and 599 ± 69 vs. 987 ± 153 ml/min in WHHL and control rabbits, respectively; P < 0.05 for both). No differences were observed in the AMP parameters.
BPAP Km and Amax values were
estimated separately under mixed-order reaction conditions. No
differences in Km values were found (9.79 ± 1 vs. 9.9 ± 1.31 µM), whereas WHHL rabbit Amax was
significantly decreased (5.29 ± 0.88 vs. 7.93 ± 0.8 µmol/min in
WHHL and control rabbits, respectively; P < 0.05). We
conclude that the observed pulmonary endothelial ACE activity reduction
in WHHL rabbits appears related to a decrease in enzyme mass rather
than to alterations in enzyme affinity.
Watanabe heritable hyperlipidemic; 5'-nucleotidase; pulmonary
circulation; endothelium
