Reduced lung endothelial angiotensin-converting enzyme activity in Watanabe hyperlipidemic rabbits in vivo

We investigated pulmonary endothelial function in vivo in 12- to 18-mo-old male Watanabe heritable hyperlipidemic (WHHL; n = 7) and age- and sex-match ed New Zealand White (n = 8) rabbits. The animals were anesthetized and art ificially ventilated, and the chest was opened and put in total heart bypas s. The single-pass transpulmonary utilizations of the angiotensin-convertin g enzyme (ACE) substrate [H-3]benzoyl-Phe-Ala-Pro (BPAP) and the 5'-nucleot idase (NCT) substrate [C-14]AMP were estimated, and the first-order reactio n parameter A(max)/K-m, where A(max) is the product of enzyme mass and the catalytic rate constant and K-m is the Michaelis-Menten constant, was calcu lated. BPAP transpulmonary utilization and A(max)/K-m were reduced in WHHL (1.69 +/- 0.16 vs. 2.9 +/- 0.44 and 599 +/- 69 vs. 987 +/- 153 ml/min in WH HL and control rabbits, respectively; P < 0.05 for both). No differences we re observed in the AMP parameters. BPAP K-m and A(max) values were estimate d separately under mixed-order reaction conditions. No differences in K-m v alues were found (9.79 +/- 1 vs. 9.9 +/- 1.31 mu M), whereas WHHL rabbit A( max) was significantly decreased (5.29 +/- 0.88 vs. 7.93 +/- 0.8 mu mol/min in WHHL and control rabbits, respectively; P, 0.05). We conclude that the observed pulmonary endothelial ACE activity reduction in WHHL rabbits appea rs related to a decrease in enzyme mass rather than to alterations in enzym e affinity.