Angiotensin II metabolism by tissues from developing rats

Asp¹-¹²⁵I-Tyr⁴-angiotensin II (¹²⁵I-AII) was degraded during incubation with rat plasma or homogenates of liver or kidney. The electrophoretic profile of peptide fragments revealed that the disappearance of ¹²⁵I-AII was first order and was accompanied by an accumulation of ¹²⁵I-tyrosine in the incubation medium. The only other metabolites of angiotensin AII detectable by peptide mapping were the amino-terminus tetrapeptide and the carboxyterminus hexapeptide. The appearance of these fragments was highly variable, suggesting that endopeptidases did not constitute the ultimate cleavage of angiotensin II hydrolysis. The half-life of ¹²⁵-AII in plasma or liver homogenates did not change with age (approximately 8 to 12 and 6 to 9 min, respectively). In contrast, the rate of disappearance of ¹²⁵I-AII in homogenates of rat kidney depended upon the age of the rat from which the tissue was obtained. The half-life of ¹²⁵I-AII decreased three-fold (from approximately 8.3 to 2.8 min) between 2 wk after birth and adult (approximately 8 wk). This increase in the rat of metabolism of ¹²⁵I-AII was accompanied by a concomitant two-fold, age-related increase in the rate of appearance of ¹²⁵I-tyrosine in the reaction mixture containing renal tissue.