Fate of labeled angiotensin II microinfused into individual nephrons in the rat

Abstract

14C-labeled angiotensin II ([14C]AII) and tritiated inulin ([3H]In) were infused into individual nephrons in Inactin-anesthetized rats and urinary excretion was measured. Site of infusion was identified by neoprene injection and microdissection. In other experiments with higher doses of [14C]AII, microperfused at 10-4-10-5 M (concentrations 10-5-10-6 higher than contained in plasma), [14C]AII and its urinary metabolites were identified and quantified by two-dimensional peptide mapping. Recovery of 14C was 10.9% when proximal tubules were infused and 94.8% when distal tubules were infused. There was no correlation with tubular length in either case. For proximal tubules, two-thirds of the 11% recovered from urine appeared as peptide fragments of AII. With distal tubules almost all 14C activity appeared as intact AII. The principal metabolic product recovered from urine after proximal injection was the chymotryptic peptide, and its recovery was inversely related to tubular length. It is suggested that rapid removal of [14C]AII by proximal tubular cells occurs by enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder