Formation of [Des-Asp¹]Angiotensin I by the Perfused Rat Lung*

Abstract

Bioassay studies have indicated that angiotensin I (Ang I), but not angiotensin II (Ang II), is degraded by the intact lung. The present study was an attempt to isolate and quantify pulmonary metabolites of Ang I. The pulmonary vascular bed of the rat was isolated and perfused at 4-6 ml/min (< 20 mm Hg) with oxygenated Krebs buffer containing 5% bovine serum albumin. [3H-Leu10]Ang I (3-10 ng) was administered, and pulmonary effluent samples were collected every 15 sec for 5 min. Peptides were isolated by Dowex chromatography and separated by thin layer chromatography. 3H-labeled peptides were eluted from the thin layer chromatography plate, and the Ang I and [des-Asp1]Ang I levels were estimated by RIA. These peptides were shown to be hydrolyzed by purified converting enzyme with the release of His-3H-Leu. About 25% of the [3H]Ang I administered was isolated as [3H-des-Asp1]Ang I, and this percentage increased to 33% after treatment with teprotide. These studies clearly demonstrate that [des-Asp1]Ang I is a major pulmonary metabolite of Ang I and suggest the presence of a pulmonary aminopeptidase which hydrolyzes Ang I but not Ang II.

Angiotensin I, II, and III in sheep. A model of angiotensin production and metabolism.

“…From qualitative studies in sheep reported earlier, 31 -M it was suggested that the concentration of All in venous blood was small. Using more sophisticated methodology and especially recovery tracers, we have shown here that the arterial and central venous profiles are very similar.…”