title: Reduced lung endothelial angiotensin-converting enzyme activity in Watanabe hyperlipidemic rabbits in vivo.
abstract: 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 [(3)H]benzoyl-Phe-Ala-Pro (BPAP) and the 5'-nucleotidase (NCT) substrate [(14)C]AMP were estimated, and the first-order reaction 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 calculated. 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 WHHL and control rabbits, respectively; P < 0.05 for both). No differences were observed in the AMP parameters. BPAP K(m) and A(max) values were estimated separately under mixed-order reaction conditions. No differences in K(m) values were found (9.79 +/- 1 vs. 9.9 +/- 1.31microM), whereas WHHL rabbit A(max) was significantly decreased (5.29 +/- 0.88 vs. 7. 93 +/- 0.8 micromol/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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, 30912, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: J B
authors.initials: JB
authors.lastname: Parkerson
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: E L
authors.initials: EL
authors.lastname: Fisher
authors.forename: C
authors.initials: C
authors.lastname: Glynos
authors.forename: A
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: R G
authors.initials: RG
authors.lastname: Gerrity
authors.forename: J D
authors.initials: JD
authors.lastname: Catravas
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D004727:Endothelium / Q000201:enzymology; D006949:Hyperlipidemias / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits
chemical_list: D009842:Oligopeptides; D000249:Adenosine Monophosphate; C029689:benzoylphenylalanyl-alanyl-proline; D015720:5'-Nucleotidase; D007703:Peptidyl-Dipeptidase A