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. 1980 Sep;77(9):5476–5479. doi: 10.1073/pnas.77.9.5476

Specific inhibition of renin by an angiotensinogen analog: studies in sodium depletion and renin-dependent hypertension.

J Burton, R J Cody Jr, J A Herd, E Haber
PMCID: PMC350083  PMID: 6159648

Abstract

The angiotensin substrate analog Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys has no significant effect on blood pressure in sodium-replete monkeys (Macaca fascicularis) but blocks the pressor response to infused human renin. Pressor responses to angiotensin I and angiotensin II are not attenuated. In five studies in sodium-depleted monkeys, an infusion of 2 mg of the peptide per kg of body weight resulted in a reduction of mean arterial pressure (MAP) from 105 +/- 4 to 79 +/- 3 mm Hg, which is not significantly different from the response to 1 mg of the angiotensin I-converting enzyme inhibitor teprotide per kg. In uninephrectomized monkeys, inflation of a suprarenal aortic cuff caused an increase in MAP from 107 +/- 3 to 131 +/- 3 mm Hg. Infusion of 0.6 mg of the renin-inhibitory peptide per kg was followed by a return of blood pressure to 107 +/- 4 mm Hg--a depressor response similar to that observed with teprotide. This specific in vivo inhibitor of renin can now be applied to a wide variety of physiologic studies.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burton J., Poulsen K., Haber E. Competitive inhibitors of renin. Inhibitors effective at physiological pH. Biochemistry. 1975 Aug 26;14(17):3892–3898. doi: 10.1021/bi00688a024. [DOI] [PubMed] [Google Scholar]
  2. Coleman T. G., Cowley A. W., Jr, Guyton A. C. Angiotensin and the hemodynamics of chronic salt deprivation. Am J Physiol. 1975 Jul;229(1):167–171. doi: 10.1152/ajplegacy.1975.229.1.167. [DOI] [PubMed] [Google Scholar]
  3. Cushman D. W., Cheung H. S., Sabo E. F., Ondetti M. A. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry. 1977 Dec 13;16(25):5484–5491. doi: 10.1021/bi00644a014. [DOI] [PubMed] [Google Scholar]
  4. Dzau V. J., Kopelman R. I., Barger A. C., Haber E. Renin-specific antibody for study of cardiovascular homeostasis. Science. 1980 Mar 7;207(4435):1091–1093. doi: 10.1126/science.6986653. [DOI] [PubMed] [Google Scholar]
  5. Evin G., Gardes J., Kreft C., Castro B., Corvol P., Menard J. Soluble pepstatins: a new approach to blockade in vivo of the renin-angiotensin system. Clin Sci Mol Med Suppl. 1978 Dec;4:167s–169s. [PubMed] [Google Scholar]
  6. Gavras H., Brunner H. B., Vaughan E. D., Laragh J. H. Angiotensin-sodium interaction in blood pressure maintenance of renal hypertensive and normotensive rats. Science. 1973 Jun 29;180(4093):1369–1371. doi: 10.1126/science.180.4093.1369. [DOI] [PubMed] [Google Scholar]
  7. Haber E., Burton J. Inhibitors of renin and their utility in physiologic studies. Fed Proc. 1979 Dec;38(13):2768–2773. [PubMed] [Google Scholar]
  8. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  9. Keim G. R., Jr, Kirpan J., Peterson A. E., Murphy B. F., Hassert G. L., Jr, Poutsiaka J. W. Inhibition of angiotensin I-initiated hemodynamic changes in anesthetized dogs by a synthetic nonapeptide. Proc Soc Exp Biol Med. 1972 May;140(1):149–152. doi: 10.3181/00379727-140-36413. [DOI] [PubMed] [Google Scholar]
  10. Khosla M. C., Hall M. M., Smeby R. R., Bumpus F. M. Agonist and antagonist relationships in 1- and 8-substituted analogs of angiotensin II. J Med Chem. 1974 Nov;17(11):1156–1160. doi: 10.1021/jm00257a006. [DOI] [PubMed] [Google Scholar]
  11. Ondetti M. A., Rubin B., Cushman D. W. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science. 1977 Apr 22;196(4288):441–444. doi: 10.1126/science.191908. [DOI] [PubMed] [Google Scholar]
  12. Ondetti M. A., Williams N. J., Sabo E. F., Pluscec J., Weaver E. R., Kocy O. Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry. 1971 Oct 26;10(22):4033–4039. doi: 10.1021/bi00798a004. [DOI] [PubMed] [Google Scholar]
  13. Samuels A. I., Miller E. D., Jr, Fray J. C., Haber E., Barger A. C. Renin--angiotensin antagonists and the regulation of blood pressure. Fed Proc. 1976 Nov;35(13):2512–2520. [PubMed] [Google Scholar]
  14. Scriabine A. Beta-adrenoceptor blocking drugs in hypertension. Annu Rev Pharmacol Toxicol. 1979;19:269–284. doi: 10.1146/annurev.pa.19.040179.001413. [DOI] [PubMed] [Google Scholar]
  15. Swartz S. L., Williams G. H., Hollenberg N. K., Moore T. J., Dluhy R. G. Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. Hypertension. 1979 Mar-Apr;1(2):106–111. doi: 10.1161/01.hyp.1.2.106. [DOI] [PubMed] [Google Scholar]

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