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Captopril removal by rabbit lung in vivo
Biochemical Pharmacology
|July 1, 1985
Summary
Pulmonary removal of captopril in rabbits is saturable, suggesting it binds to lung endothelial angiotensin converting enzyme (ACE). This binding capacity decreases with higher captopril doses and can be reduced by a competing ACE substrate.
Area of Science:
- Pharmacology
- Pulmonary Physiology
- Biochemistry
Background:
- Captopril is an angiotensin converting enzyme (ACE) inhibitor.
- The lungs play a role in drug metabolism and removal.
- Understanding captopril's pulmonary fate is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the mechanism and capacity of pulmonary captopril removal in vivo.
- To determine if captopril removal is saturable and influenced by ACE activity.
- To assess the interaction between captopril and pulmonary ACE.
Main Methods:
- Multiple indicator dilution technique in anesthetized rabbits.
- Coinjection of [14C]captopril and indocyanine green (ICG) into the jugular vein.
- Serial blood sampling from the carotid artery to measure substance concentrations.
Main Results:
- Pulmonary removal of captopril was dose-dependent and saturable.
- Higher captopril doses (70 nmol/kg) showed significantly lower removal than lower doses (10 nmol/kg).
- Pulmonary metabolism of an ACE substrate ([3H]BPAP) was inhibited by captopril, and competing ACE substrate reduced captopril removal.
Conclusions:
- Pulmonary removal of captopril in vivo is a saturable process.
- This removal likely involves binding to pulmonary endothelial ACE.
- Captopril's interaction with pulmonary ACE influences its own removal and the metabolism of other ACE substrates.