Micropuncture evidence of rapid hydrolysis of bradykinin by rat proximal tubule

Abstract

3H-labeled bradykinin ([3H]BKN) and 14C-labeled inulin ([14C]In) were simultaneously microinfused into proximal or distal tubules in Inactin-anesthetized rats, and urinary excretion and tubular transit times were measured. In other experiments higher doses of [3H]BKN were microinfused and intact peptide and its metabolites identified and quantified by two-dimensional peptide mapping. The site of infusion was identified by neoprene injection and microdissection. Urinary recovery of 3H label was 24.1% when proximal tubules were infused and 98.0% when distal tubules were infused. For proximal tubules, 85% of 3H activity recovered from urine consisted of metabolites (81%[3H]Pro and 4% [3H]Arg1-Phe5) and 15% was intact BKN. Urinary recoveries of [3H]BKN and metabolites were unrelated to tubular length. With distal tubules all 3H activity appeared as intact BKN. Excretion curves of simultaneously infused [3H]BKN and [14C]In showed no marked differences in configuration for either proximal or distal or distal tubules. We suggested that removal of [3H]BKN by proximal tubular cells occurs by rapid enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder.