Mechanism of Renal Handling of Angiotensin II in the Dog

The mechanism of renal handling of angiotensin II was studied in vivo in the renal circulation of the intact anesthetized dog and in vitro in whole blood using 14 C-5-Ile-angiotensin II, l -Asp- 125 I-angiotensin II, and d -Asp- 125 I-angiotensin II. Seventy-five percent of a 600-pmole bolus of 14 C-angiotensin II was degraded in a single passage through the kidney as measured by radioactive tracer and radioimmunoassay techniques. The metabolic products were 14 C-5-Ile (59%), 5-Ile-8-Phe (15%), and 3-Val-8-Phe (2%); recovery of the injected radioactive material was 99%. The degradation rate of 14 C-angiotensin II in whole dog blood in vitro was only 17%/min. Similar metabolic patterns were seen in vivo and in vitro. Sixty-six percent of the injected l -Asp- 125 I-angiotensin II was metabolized, but only 23% of the d -Asp- 125 I-angiotensin II was metabolized in a single passage through the kidney. These observations indicate that, under the conditions of these experiments, (1) angiotensin II is rapidly metabolized in the dog kidney by multiple enzymes, including an aminopeptidase, (2) circulating plasma enzymes do not account for the renal handling of angiotensin II, and (3) angiotensin II is not sequestered in the kidney.