Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Dec;116(7):2963–2970. doi: 10.1111/j.1476-5381.1995.tb15951.x

Comparative effects of angiotensin II and its degradation products angiotensin III and angiotensin IV in rat aorta.

Q Li 1, L Zhang 1, M Pfaffendorf 1, P A van Zwieten 1
PMCID: PMC1909200  PMID: 8680731

Abstract

1. In the present study, the contractile effects of angiotensin III (AIII) and angiotensin IV (AIV) compared with those of angiotensin II (AII) were determined in rat aortic ring preparations. 2. All three peptides caused concentration-dependent contractions with similar maximal responses. AIII proved approximately 4 times less potent than AII, whereas AIV was about 1000 times less active than AII. 3. The selective AT1-receptor antagonist, losartan (10-300 nM) caused parallel rightward shifts of the concentration-response curves (CRC) for all three peptides. The Schild plot slopes for the effect of losartan on AIII curves were significantly lower than unity (P < 0.05). The selective AT2-receptor antagonist, PD123177 did not influence the CRCs for AII and AIV. However, the AIII curves were moderately shifted leftward in the presence of PD123177 (0.1 and 1 microM). 4. Destruction of the endothelium or incubation with the NO-synthesis inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) (0.1 mM) significantly enhanced the contractile responses to all three peptides. 5. Tachyphylaxis was investigated by constructing a second CRC for all three peptides, after an interval of 1 h. The presence of endothelium significantly enhanced the development of tachyphylaxis to all three peptides. However, in endothelium-denuded preparations, the Emax value of the second curve elicited by AII was about 50%, compared with the first one, whereas for AIII and AIV Emax values were as high as 90% and 100%, respectively. 6. Our results indicate that both AIII and AIV are less potent but similarly efficacious vasoconstrictor agents compared with AII. Their contractile effects are also mediated by AT1-receptors and probably modulated by endothelium. Tachyphylaxis induced by AIII and AIV proved weaker than that for AII. Tachyphylaxis appears to be enhanced by the presence of an intact endothelium.

Full text

PDF
2963

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abdelrahman A., Pang C. C. Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan. Can J Physiol Pharmacol. 1992 May;70(5):716–719. doi: 10.1139/y92-093. [DOI] [PubMed] [Google Scholar]
  3. Abhold R. H., Harding J. W. Metabolism of angiotensins II and III by membrane-bound peptidases from rat brain. J Pharmacol Exp Ther. 1988 Apr;245(1):171–177. [PubMed] [Google Scholar]
  4. Ahmad S., Ward P. E. Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins. J Pharmacol Exp Ther. 1990 Feb;252(2):643–650. [PubMed] [Google Scholar]
  5. Boulay G., Servant G., Luong T. T., Escher E., Guillemette G. Modulation of angiotensin II binding affinity by allosteric interaction of polyvinyl sulfate with an intracellular domain of the DuP-753-sensitive angiotensin II receptor of bovine adrenal glomerulosa. Mol Pharmacol. 1992 Apr;41(4):809–815. [PubMed] [Google Scholar]
  6. Bumpus F. M., Catt K. J., Chiu A. T., DeGasparo M., Goodfriend T., Husain A., Peach M. J., Taylor D. G., Jr, Timmermans P. B. Nomenclature for angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research. Hypertension. 1991 May;17(5):720–721. doi: 10.1161/01.hyp.17.5.720. [DOI] [PubMed] [Google Scholar]
  7. Buxton I. L., Cheek D. J., Eckman D., Westfall D. P., Sanders K. M., Keef K. D. NG-nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists. Circ Res. 1993 Feb;72(2):387–395. doi: 10.1161/01.res.72.2.387. [DOI] [PubMed] [Google Scholar]
  8. Chang R. S., Lotti V. J. Angiotensin receptor subtypes in rat, rabbit and monkey tissues: relative distribution and species dependency. Life Sci. 1991;49(20):1485–1490. doi: 10.1016/0024-3205(91)90048-g. [DOI] [PubMed] [Google Scholar]
  9. Chen L., McNeill J. R., Wilson T. W., Gopalakrishnan V. Heterogeneity in vascular smooth muscle responsiveness to angiotensin II. Role of endothelin. Hypertension. 1995 Jul;26(1):83–88. doi: 10.1161/01.hyp.26.1.83. [DOI] [PubMed] [Google Scholar]
  10. Cheng D. Y., DeWitt B. J., Dent E. L., Nossaman B. D., Kadowitz P. J. Analysis of responses to angiotensin IV in the pulmonary vascular bed of the cat. Eur J Pharmacol. 1994 Aug 11;261(1-2):223–227. doi: 10.1016/0014-2999(94)90324-7. [DOI] [PubMed] [Google Scholar]
  11. Chiu A. T., Herblin W. F., McCall D. E., Ardecky R. J., Carini D. J., Duncia J. V., Pease L. J., Wong P. C., Wexler R. R., Johnson A. L. Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun. 1989 Nov 30;165(1):196–203. doi: 10.1016/0006-291x(89)91054-1. [DOI] [PubMed] [Google Scholar]
  12. Fitzsimons J. T. The effect on drinking of peptide precursors and of shorter chain peptide fragments of angiotensin II injected into the rat's diencephalon. J Physiol. 1971 Apr;214(2):295–303. doi: 10.1113/jphysiol.1971.sp009433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fujimoto M., Mihara S., Shigeri Y., Itazaki K. Possible implication of peptidase activity in different potency of angiotensins II and III for displacing [125I]angiotensin II binding in pig aorta. Eur J Pharmacol. 1992 May 14;215(2-3):259–264. doi: 10.1016/0014-2999(92)90036-4. [DOI] [PubMed] [Google Scholar]
  14. Gruetter C. A., Ryan E. T., Lemke S. M., Bailly D. A., Fox M. K., Schoepp D. D. Endothelium-dependent modulation of angiotensin II-induced contraction in blood vessels. Eur J Pharmacol. 1988 Jan 27;146(1):85–95. doi: 10.1016/0014-2999(88)90489-x. [DOI] [PubMed] [Google Scholar]
  15. Gruetter C. A., Ryan E. T., Schoepp D. D. Endothelium enhances tachyphylaxis to angiotensins II and III in rat aorta. Eur J Pharmacol. 1987 Nov 3;143(1):139–142. doi: 10.1016/0014-2999(87)90745-x. [DOI] [PubMed] [Google Scholar]
  16. Haberl R. L., Decker P. J., Einhäupl K. M. Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles. Circ Res. 1991 Jun;68(6):1621–1627. doi: 10.1161/01.res.68.6.1621. [DOI] [PubMed] [Google Scholar]
  17. Hanesworth J. M., Sardinia M. F., Krebs L. T., Hall K. L., Harding J. W. Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes. J Pharmacol Exp Ther. 1993 Aug;266(2):1036–1042. [PubMed] [Google Scholar]
  18. Harding J. W., Wright J. W., Swanson G. N., Hanesworth J. M., Krebs L. T. AT4 receptors: specificity and distribution. Kidney Int. 1994 Dec;46(6):1510–1512. doi: 10.1038/ki.1994.432. [DOI] [PubMed] [Google Scholar]
  19. Kuttan S. C., Sim M. K. Angiotensin II-induced tachyphylaxis in aortas of normo- and hypertensive rats: changes in receptor affinity. Eur J Pharmacol. 1993 Mar 2;232(2-3):173–180. doi: 10.1016/0014-2999(93)90771-9. [DOI] [PubMed] [Google Scholar]
  20. Lo M., Liu K. L., Lantelme P., Sassard J. Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats. J Clin Invest. 1995 Mar;95(3):1394–1397. doi: 10.1172/JCI117792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller-Wing A. V., Hanesworth J. M., Sardinia M. F., Hall K. L., Wright J. W., Speth R. C., Grove K. L., Harding J. W. Central angiotensin IV binding sites: distribution and specificity in guinea pig brain. J Pharmacol Exp Ther. 1993 Sep;266(3):1718–1726. [PubMed] [Google Scholar]
  22. Moore A. F., HAll M. M., Khairallah P. A. A comparison of the effects of angiotensin II and heptapeptide on smooth muscle (vascular and uterine). Eur J Pharmacol. 1976 Sep;39(1):101–107. doi: 10.1016/0014-2999(76)90117-5. [DOI] [PubMed] [Google Scholar]
  23. Murphy T. J., Nakamura Y., Takeuchi K., Alexander R. W. A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors. Mol Pharmacol. 1993 Jul;44(1):1–7. [PubMed] [Google Scholar]
  24. Nossaman B. D., Feng C. J., Kaye A. D., Kadowitz P. J. Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat. Am J Physiol. 1995 Feb;268(2 Pt 1):L302–L308. doi: 10.1152/ajplung.1995.268.2.L302. [DOI] [PubMed] [Google Scholar]
  25. Oliver J. A., Sciacca R. R. Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat. J Clin Invest. 1984 Oct;74(4):1247–1251. doi: 10.1172/JCI111534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Oshiro M. E., Shimuta S. I., Paiva T. B., Paiva A. C. Evidence for a regulatory site in the angiotensin II receptor of smooth muscle. Eur J Pharmacol. 1989 Aug 3;166(3):411–417. doi: 10.1016/0014-2999(89)90353-1. [DOI] [PubMed] [Google Scholar]
  27. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  28. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  29. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  30. Papadimitriou A., Worcel M. Dose-response curves for angiotensin II and synthetic analogues in three types of smooth muscle: existence of different forms of receptor sites for angiotensin II. Br J Pharmacol. 1974 Feb;50(2):291–297. doi: 10.1111/j.1476-5381.1974.tb08575.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Peach M. J. Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev. 1977 Apr;57(2):313–370. doi: 10.1152/physrev.1977.57.2.313. [DOI] [PubMed] [Google Scholar]
  32. Pendleton R. G., Gessner G., Horner E. Comparative effects of angiotensin II and angiotensin III in rabbit adrenal and aortic tissues. J Pharmacol Exp Ther. 1991 Feb;256(2):614–620. [PubMed] [Google Scholar]
  33. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Robertson M. J., Cunoosamy M. P., Clark K. L. Effects of peptidase inhibition on angiotensin receptor agonist and antagonist potency in rabbit isolated thoracic aorta. Br J Pharmacol. 1992 May;106(1):166–172. doi: 10.1111/j.1476-5381.1992.tb14310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Scheuer D. A., Perrone M. H. Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin. Am J Physiol. 1993 May;264(5 Pt 2):R917–R923. doi: 10.1152/ajpregu.1993.264.5.R917. [DOI] [PubMed] [Google Scholar]
  36. Shimuta S. I., Kanashiro C. A., Ferreira A. T., Oshiro M. E., Paiva T. B., Paiva A. C. Role of Na+ and protein kinase C in angiotensin desensitization and tachyphylaxis in the guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol. 1993 Apr;347(4):425–431. doi: 10.1007/BF00165394. [DOI] [PubMed] [Google Scholar]
  37. Sim M. K., Radhakrishnan R. In vivo study of angiotensin II tachyphylaxis in freely moving normo- and hypertensive rats. Pharmacol Toxicol. 1994 Apr-May;74(4-5):223–227. doi: 10.1111/j.1600-0773.1994.tb01102.x. [DOI] [PubMed] [Google Scholar]
  38. Smith R. D., Chiu A. T., Wong P. C., Herblin W. F., Timmermans P. B. Pharmacology of nonpeptide angiotensin II receptor antagonists. Annu Rev Pharmacol Toxicol. 1992;32:135–165. doi: 10.1146/annurev.pa.32.040192.001031. [DOI] [PubMed] [Google Scholar]
  39. Thorin E., Atkinson J. Modulation by the endothelium of sympathetic vasoconstriction in an in vitro preparation of the rat tail artery. Br J Pharmacol. 1994 Jan;111(1):351–357. doi: 10.1111/j.1476-5381.1994.tb14067.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Timmermans P. B., Wong P. C., Chiu A. T., Herblin W. F., Benfield P., Carini D. J., Lee R. J., Wexler R. R., Saye J. A., Smith R. D. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993 Jun;45(2):205–251. [PubMed] [Google Scholar]
  41. Timmermans P. B., Wong P. C., Chiu A. T., Herblin W. F. Nonpeptide angiotensin II receptor antagonists. Trends Pharmacol Sci. 1991 Feb;12(2):55–62. doi: 10.1016/0165-6147(91)90498-h. [DOI] [PubMed] [Google Scholar]
  42. Toda N., Miyazaki M. Regional and species differences in the response of isolated arteries to angiotnesin II. Jpn J Pharmacol. 1978 Jun;28(3):495–497. doi: 10.1254/jjp.28.495. [DOI] [PubMed] [Google Scholar]
  43. Tonnaer J. A., Wiegant V. M., de Jong W., De Wied D. Central effects of angiotensins on drinking and blood pressure: structure-activity relationships. Brain Res. 1982 Mar 25;236(2):417–428. doi: 10.1016/0006-8993(82)90725-9. [DOI] [PubMed] [Google Scholar]
  44. Viswanathan M., Tsutsumi K., Correa F. M., Saavedra J. M. Changes in expression of angiotensin receptor subtypes in the rat aorta during development. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1361–1367. doi: 10.1016/0006-291x(91)91723-p. [DOI] [PubMed] [Google Scholar]
  45. Whitebread S., Mele M., Kamber B., de Gasparo M. Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun. 1989 Aug 30;163(1):284–291. doi: 10.1016/0006-291x(89)92133-5. [DOI] [PubMed] [Google Scholar]
  46. Zhang J., Pfaffendorf M., Zhang J. S., van Zwieten P. A. Influence of the vascular endothelium on angiotensin II-induced contractions in rabbit renal artery. Fundam Clin Pharmacol. 1995;9(1):25–29. doi: 10.1111/j.1472-8206.1995.tb00261.x. [DOI] [PubMed] [Google Scholar]
  47. Zhang J., Van Meel J. C., Pfaffendorf M., Zhang J., Van Zwieten P. A. Endothelium-dependent, nitric oxide-mediated inhibition of angiotensin II-induced contractions in rabbit aorta. Eur J Pharmacol. 1994 Sep 12;262(3):247–253. doi: 10.1016/0014-2999(94)90738-2. [DOI] [PubMed] [Google Scholar]
  48. van Heiningen P. N., van Zwieten P. A. Influence of the endothelium on Ca2+ dependency of angiotensin II-induced contractions of rat aortic rings. Fundam Clin Pharmacol. 1993;7(5):227–233. doi: 10.1111/j.1472-8206.1993.tb00236.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES