In vivo and in vitro conversion of des-1-Asp angiotensin I to angiotensin III.

Abstract The conversion of exogenous des-Asp angiotensin I to des-Asp angiotensin II (angiotensin III) was studied in vivo in the pulmonary circulation of the intact pentobarbital-anesthetized dog and in vitro in whole blood and heparin-treated plasma by fractionation of 125 I-labeled peptides and by radioimmunoassay. Conversion and hydrolysis of [ 125 I]des-Asp angiotensin I and [ 125 I]angiotensin I were compared in vitro and in vivo . The time course of conversion of des-Asp angiotensin I to angiotensin III in vitro was more rapid than that of angiotensin I to II, but the peak concentration of angiotensin III generated was less than angiotensin II due to the more rapid hydrolysis of the des-Asp peptides. Injection of des-Asp angiotensin I into the right atrium was associated with a pressor response and with the appearance of a small amount of angiotensin III in aortic blood. SQ20881 (a nonapeptide converting enzyme inhibitor) abolished both the pressor response and the generation of angiotensin III. After injection of [ 125 I]des-Asp angiotensin I, only 10 per cent of the labeled material appearing in arterial blood was angiotensin III; 15 per cent was unchanged des-Asp angiotensin I; 15 per cent was an unidentified metabolite; and 60 per cent was tyrosine. This contrasts with the pattern of peptides recovered after injection of [ 125 I]angiotensin I: 70 per cent angiotensin II, 20 per cent intact angiotensin I and only 10 per cent peptide metabolites and tyrosine. Results indicate that conversion of des-Asp angiotensin I to angiotensin III does occur in the pulmonary circulation of the dog but that hydrolysis of the des-Asp peptides by angiotensinases is so rapid that little circulating angiotensin II and only a small pressor response appear. The data suggest that pulmonary conversion of des-Asp angiotensin I is not an important source of circulating angiotensin III in the dog.