Captopril removal by rabbit lung in vivo.
Removal of [14C]captopril by the lungs of anesthetized rabbits was measured by the multiple indicator dilution technique. After coinjection of indocyanine green (ICG) and [14C]captopril into the jugular vein of anesthetized rabbits, serial blood samples were collected from the carotid artery and each was analyzed for its content of both substances. Percent removal (R) of captopril after its initial injection of 10 nmoles captopril/kg (calculated at the peak of the ICG outflow curve) was 40.2 +/- 2.5 (S.E.M.) and was significantly greater than R after a second injection of 10 nmoles captopril/kg (20.1 +/- 2.4) 1 hr later. Removal of 70 nmoles captopril/kg (5.8 +/- 3.0 after first injection, 6.4 +/- 2.2 after second injection) was significantly lower than R of 10 nmoles captopril/kg. During a single pulmonary passage of either dose of captopril, R was inversely related to the calculated fractional concentration of intravascular captopril. Pulmonary metabolism of the angiotensin converting enzyme (ACE) substrate [3H]benzoyl-Phe-Ala-Pro [( 3H]BPAP) was 70.1 +/- 1.7% in the absence of captopril, and was reduced significantly to 27.4 +/- 2.4% by 10 nmoles captopril/kg and 7.6 +/- 0.2% by 6 mumoles BPAP/kg. BPAP (6.4 +/- 0.6 mumoles/kg) significantly reduced R of the first and second injections of 10 nmoles captopril/kg but this effect was selective, since BPAP did not reduce pulmonary removal of [14C]serotonin. These data indicate that pulmonary removal of captopril in vivo is saturable and may primarily reflect binding of the drug to pulmonary endothelial ACE.
Howell
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Moalli
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Gillis
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D000818:Animals; D002216:Captopril / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D011392:Proline / Q000031:analogs & derivatives*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism
D002250:Carbon Radioisotopes; D009842:Oligopeptides; D012701:Serotonin; C029689:benzoylphenylalanyl-alanyl-proline; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A