Showing papers by "Suzanne Oparil published in 1973"
TL;DR: Observations indicate that 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) angioten II is not sequestered in the kidney.
Abstract: 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 14C-5-Ile-angiotensin II, l-Asp-125I-angiotensin II, and d-Asp-125I-angiotensin II. Seventy-five percent of a 600-pmole bolus of 14C-angiotensin II was degraded in a single passage through the kidney as measured by radioactive tracer and radioimmunoassay techniques. The metabolic products were 14C-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 14C-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-125I-angiotensin II was metabolized, but only 23% of the d-Asp-125I-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...
32 citations
TL;DR: Results indicate that the enzymatic binding sites for AI-converting enzyme in vivo and in vitro extend from position 10 to position 8 but not to position 7, and D-amino acid substitution at positions 7 and 5 abolishes biologic and immunologic activity without interfering with conversion.
Abstract: The substrate requirements for angiotensin I-converting enzyme were studied in vivo in the dog lung and in vitro in plasma, using angiotensin I (AI), 5-D-Ile-AI, 7-D-Pro-AI, and 8-D-Phe-AI which had been synthesized by the solid-phase technique. All peptides were inactive in the rabbit aortic strip preparation. None of the D-amino acid-substituted peptides gave a pressor response in the anesthetized dog; none showed significant immunologic cross-reactivity with anti-AI serum or antiangiotensin II serum. Each peptide was labeled with 125I, and the monoiodinated species was isolated. The iodinated peptides were incubated with diluted dog plasma or injected into the right ventricle of intact anesthetized dogs. In vitro, 125I-AI, 125I-5-D-IIe-AI, and 125I-7-D-Pro-AI were converted to angiotensin II (AII). 8-D-Phe-AI was not converted. In vivo, 15 seconds after injecting 125I-AI, 125I-5-D-IIe-AI, or 125I-7-D-Pro-AI into the right ventricle, 125I-AJI accounted for 70, 60, and 45%, respectively, of the radioacti...
18 citations