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

Stylianos E. Orfanos, James B. Parkerson, Xilin Chen, Eugene L. Fisher, Constantinos Glynos, Andreas Papapetropoulos, Ross G. Gerrity, John D. Catravas

Research output: Contribution to journalArticle

3 Scopus citations

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 [3H]benzoyl-Phe-Ala-Pro (BPAP) and the 5'- nucleotidase (NCT) substrate [14C]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 ± 69vs. 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 ± 1.31 μM), whereas WHHL rabbit A(max) 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.

Original languageEnglish (US)
Pages (from-to)L1280-L1288
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number6 22-6
DOIs
StatePublished - Jun 2000

Keywords

  • 5'-nucleotidase
  • Endothelium
  • Pulmonary circulation
  • Watanabe heritable hyperlipidemic

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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