Pulmonary angiotensin-converting enzyme kinetics after acute lung injury in the rabbit.
Depression of lung endothelial cell metabolic function may be an early and sensitive indicator of lung damage. When such functions are measured in vivo, substrates injected usually must be limited to "trace" doses due to the significant hemodynamic effects of high doses of substrate. Under first-order conditions (i.e., trace doses) the enzyme or transport system rate constant Vmax/Km may be calculated, but independent estimates of each variable (Vmax and Km) are not available. We therefore used multiple indicator-dilution methods and higher substrate concentrations to apply a mathematical model, based on saturable kinetics that yield independent estimates of the apparent kinetic parameters Vmax and Km for pulmonary angiotensin-converting enzyme (ACE). We used the ACE substrate, [3H]benzoyl-phenylalanyl-alanyl-proline ([3H]BPAP) and made these measurements and also estimates of serotonin [5-hydroxytryptamine (5-HT)] removal, before and after acute lung injury induced by intratracheal administration of phorbol myristate acetate (PMA). PMA significantly depressed the percent 5-HT removal (62 +/- 3 to 44 +/- 4%) and BPAP percent metabolism (74 +/- 2 to 66 +/- 2), when trace amounts of either compound were injected as a bolus.(ABSTRACT TRUNCATED AT 250 WORDS)
Riggs
D
D
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Havill
A M
AM
Pitt
B R
BR
Gillis
C N
CN
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006400:Hematocrit; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D012701:Serotonin; D002374:Catalase; D007703:Peptidyl-Dipeptidase A; D013755:Tetradecanoylphorbol Acetate