Mechanism for renal tubular handling of angiotensin

Abstract

Previous laboratory studies showed that when [5-Ile-14C]angiotensin II ([14C]AII) is microperfused through rabbit proximal straight nephron segments in vitro, [14C]Ile appears as the predominant labeled species in the collection pipette and 14C-labeled material is rapidly and extensively reabsorbed into the bathing medium. In order to evaluate the hypothesis that angiotensin is hydrolyzed at the renal brush border of proximal tubular cells followed by reabsorption of metabolites, rabbit proximal straight nephron segments were microperfused in vitro with [10-Leu-3H]angiotensin I ([3H]AI) (80.1 pg/min), and isolated microvilli from rabbit renal brush border were incubated in the presence of [3H]AI or [14C]AII. Reabsorption of 3H label was quantitifed during the microperfusion procedure and the collection fluid and bathing medium were analyzed by high-voltage paper electrophoresis to document the extent and pattern of peptide hydrolysis. Transport of 3H label into the bathing medium varied linearly with time during 30 min of perfusion and 12.4% of perfused radiolabel was reabsorbed per millimeter tubule length. [3H]Leu appeared as the only labeled metabolite in the collection fluid and bathing medium, accompanied by little or no intact [3H]AI. Incubation of [3H]AI and [14C]AII in the presence of isolated microvilli from renal brush border yielded [3H]Leu and [14C]Ile, respectively. [3H]AI and [14C]AII are apparently hydrolyzed at the brush border of the renal proximal tubule, followed by reabsorption of metabolites.