Journal of Applied Physiology, Vol 57, Issue 4 1158-1166, Copyright © 1984 by American Physiological Society
Kinetics of pulmonary angiotensin-converting enzyme activity in conscious developing lambs
B. R. Pitt and G. Lister
Apparent enzyme kinetics were determined for pulmonary
angiotensin-converting enzyme (ACE) as a function of postnatal development
and alveolar hypoxia in intact conscious lambs (9 newborn and 7 sheep, 8-23
wk). We injected into the right atrium a mixture of indocyanine green and
3H-labeled benzoyl-phenylalanyl-alanyl-proline (BPAP), a synthetic
substrate for ACE, and sampled blood from the aorta at 1-s intervals. From
this, we quantified the %BPAP metabolism during a single pass through the
lungs by use of indicator-dilution techniques. By adding unlabeled BPAP to
the injectate, combining outflow data from two to three measurements, and
applying a nonlinear model of pulmonary metabolism (J. Appl. Physiol.:
Respirat. Environ. Exercise Physiol. 51:405-414, 1981), we could determine
1) apparent maximum velocity (Vmax); 2) concentration at which velocity was
one-half Vmax (Km); and 3) alpha, a measure of perfusion heterogeneity. All
animals were studied during normoxia and while breathing 10% O2 for at
least 15 min. Seven of the newborn lambs were studied 1 wk later. Km in the
newborn was 15 +/- 3 microM and did not change significantly with age or
hypoxia. Vmax increased markedly with development (newborn: 14 +/- 2 nmol X
s-1 X g dry lung-1; sheep: 38 +/- 5 nmol X s-1 X g dry lung-1; P less than
0.01). Alveolar hypoxia significantly decreased Vmax in the newborn only (P
less than 0.05); there was no significant change in Vmax in the same animal
studied 1 wk later or in the older group.(ABSTRACT TRUNCATED AT 250 WORDS)
