In-Vivo and In-Vitro Conversion of Angiotensin I to Angiotensin II in Dog Blood

Abstract

The conversion of angiotensin I to angiotensin II was studied in vivo in the intact anesthetized dog and in vitro in whole blood and plasma treated with various anticoagulants by fractionation of radioactively labeled peptides and by radioimmunoassay. After injection of angiotensin I into the pulmonary artery at 10,000 times the physiologic level, approximately 50% of the injected material was recovered in the aorta. Fifty three percent of the material recovered had been converted to angiotensin II, as measured both by peptide release and by radioimmunoassay. Following injection of 1000 to 10,000 times physiologic levels of angiotensin I into the renal artery, 7 to 10% of the immunoreactive material in the venous effluent after a single circulation time was angiotensin II. There was no evidence of conversion in the liver or hindlimb. Conversion in vitro was far slower than in vivo, the half-life in fresh blood being 3 minutes, with longer times observed in anticoagulated plasmas. The major metabolite of in-vivo conversion was leucine, of in-vitro conversion, histidyl leucine. These observations indicate that the major site of conversion of angiotensin I to angiotensin II is in the pulmonary capillary bed. The kidnev may participate as a secondary site. Conversion in plasma probably plays no important physiologic role. The mechanism of organ and plasma conversion may differ, as indicated by the different metabolites.