Key Points
- To determine the site and mechanism of angiotensin I metabolism and conversion within the pulmonary circulation.
- Perfused radiolabeled (8-L-[(14)C] phenylalanine) angiotensin I through isolated, blood-free lungs in a single passage.
- Assessed intravascular kinetics by comparing radioactivity distribution volume and mean transit time to blue dextran.
- Tested isolated lung plasma membrane fractions for enzymatic conversion of angiotensin I to angiotensin II.
- Approximately 20% of radiolabeled angiotensin I emerged as angiotensin II after a single transpulmonary passage, while the remainder metabolized into lower homologs.
- Radioactivity was not retained in lung tissue and exhibited the same distribution volume and transit time as the intravascular marker blue dextran, demonstrating metabolism occurs at the luminal endothelial membrane.
Structured PICO
PPopulationBlood-free lungs and plasma membrane fractions of lung
IIntervention(8-L-[(14)C] phenylalanine) angiotensin I
OOutcomeMetabolism of angiotensin I to angiotensin IIsurrogate
This preclinical study provides evidence that circulating angiotensin I is metabolized to angiotensin II by enzymes on the luminal surface of pulmonary endothelial cells.