Metabolic and pharmacokinetic activity of the isolated sheep bronchial circulation

We sought to determine bronchial vascular metabolic and pharmacokinetic activity toward benzoyl-Phe-Ala-Pro (BPAP), ADP, adenosine, and prostaglandin E₂ (PGE₂) by developing an isolated sheep bronchial circulation preparation. We measured mean transit time (t̄), uptake, and metabolism by injecting ³H-labeled substrates with [¹⁴C]sucrose into the bronchial artery of sheep lungs stripped clean of parenchymal tissue. After [³H]BPAP the t̄ for ³H was the same as for ¹⁴C. Thirty-six percent of the injected BPAP was converted to metabolite ([³H]benzoyl-Phe) in a single pass. An inhibitor of angiotensin-converting enzyme, SQ 20,881, depressed BPAP metabolism by 50%, while perfusion of the bronchial circulation with glutaraldehyde reduced metabolism to a basal level. After [³H]ADP the t̄ for ³H was again the same as for ¹⁴C. ³H recovery after 40 pmol [³H]ADP was less (58%) than after 400 nmol [³H]ADP (79%). Twenty-two percent of the injected radioactivity emerged in the effluent as metabolites of ADP for either dose. Adenosine and PGE₂ uptake was negligible, and most of the recovered radioactivity in each case was unchanged substrate. This study suggests that the bronchial circulation is pharmacokinetically and metabolically active with respect to vasoactive mediators like angiotensin I, bradykinin, and adenine nucleotides, and that the enzymes responsible for this metabolic activity line the vascular lumen.