Mechanism of Pulmonary Conversion of Anglotensin II to Angiotensin II in the Dog
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Abstract
The mechanism of conversion of angiotensin I to angiotensin II was studied in vivo in the pulmonary circulation of the intact anesthetized dog and in vitro in plasma by using L-Leu-anglotensin I, D-Leu-angiotensin I, and des-Leu-angiotensin I which had been synthesized by the solid-phase technique. None of the peptides were active in the rabbit aortic strip preparation; D-Leu-angiotensin I and des-Leu-angiotensin I gave less than 5% of the pressor response of L-Leu-angiotensin I in the pentolinium-treated rat. D-Leu-angiotensin I and des-Leu-angiotensin I were not converted to angiotensin II when incubated with diluted human or dog plasma or partially purified converting enzyme from dog plasma. In a single pulmonary circulation time, following injection of a 20-nmole bolus of L-Leu-angiotensin I into the dog right ventricle, 56% of the material recovered had been converted to angiotensin II, as measured by radioimmunoassay. Conversion was accompanied by a rise in mean blood pressure of 30 mm Hg. After injection of equimolar amounts of D-Leu-angiotensin I and des-Leu-angiotensin I, no generation of angiotensin II and no pressor response occurred. These observations indicate that pulmonary conversion in vivo and plasma conversion in vitro occur via a dipepridylcarboxypeptidase and that a D-amino acid at the C-terminus prevents conversion.
- renin
- radioimmunoassay
- peptide synthesis
- carboxypeptidase
- converting enzyme
- dipeptidylcarboxypeptidase
- pulmonary circulation
- Received August 3, 1971.
- Accepted October 1, 1971.
- © 1971 American Heart Association, Inc.
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- Mechanism of Pulmonary Conversion of Anglotensin II to Angiotensin II in the DogSuzanne Oparil, Geoffery W. Tregear, Terry Koerner, Benjamin A. Barnes and Edgar HaberCirculation Research. 1971;29:682-690, originally published December 1, 1971https://doi.org/10.1161/01.RES.29.6.682
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