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. 1991 May;103(1):1057–1066. doi: 10.1111/j.1476-5381.1991.tb12300.x

Pulse exposure to protein synthesis inhibitors enhances vascular responses to des-Arg9-bradykinin: possible role of interleukin-1.

D deBlois 1, J Bouthillier 1, F Marceau 1
PMCID: PMC1908103  PMID: 1878745

Abstract

1. The modulation of the spontaneous increase in contractile responses to des-Arg9-bradykinin (des-Arg9-BK) of rabbit aortic strips incubated in vitro was studied. Rapid hypotensive responses to exogenous kinins were also measured in rabbits anaesthetized 5 h following pretreatment. 2. Continuous exposure to the protein synthesis inhibitors cycloheximide (71 microM) or anisomycin (3.8 microM) profoundly inhibited the sensitization to des-Arg9-BK in incubated aortic strips. However, temporary (3 h) inhibition of protein synthesis in vitro followed by further incubation (3 h) of tissues without inhibitor, paradoxically enhanced both the maximal contractile responses to des-Arg9-BK (1.7 microM) and the apparent affinity of the kinin without affecting contractions to noradrenaline (NA, 100 nM) at 6.5 h. 3. The stimulatory activity of the short treatment (pulse) with cycloheximide was abolished in the presence of dexamethasone sodium phosphate (100 microM throughout the incubation). The function of receptors for kinins did not appear to be altered directly by the steroid treatment. 4. Interleukin-1 beta (IL-1 beta), applied at low concentrations (100-250 pg ml-1) on aortic strips between 3 h and 6.5 h of incubation time, mimicked the selective stimulatory effect of the cycloheximide pulse on responses to des-Arg9-BK. Higher concentrations of IL-1 beta (0.5-5 ng ml-1) did not further amplify the responses to des-Arg9-BK but decreased the contractile responses to NA. 5. The modulation by IL-1 beta of vascular sensitivity to des-Arg9-BK and to NA was prevented by blockade of protein synthesis. 6. The induction in vivo by IL-1 beta (5 micrograms kg-1) or by cycloheximide (10 mg kg-1) of cardiovascular responsiveness to des-Arg9-BK was demonstrated with a blood pressure assay of exogenous kinins or with tissues isolated ex vivo 5 h after pretreatment of animals. Evidence of active disposition of cycloheximide in vivo was also obtained. 7. We propose the production of endogenous IL-1 as a possible mechanism for the enhancement of responsiveness to des-Arg9-BK observed in tissues pulsed with a protein synthesis inhibitor and for the inducing effect of cycloheximide or E. coli lipopolysaccharide in vivo. These results suggest that effects mediated by the BK1 receptor for kinins are potentially present in pathological conditions associated with IL-1 production.

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Selected References

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  1. Beasley D., Cohen R. A., Levinsky N. G. Interleukin 1 inhibits contraction of vascular smooth muscle. J Clin Invest. 1989 Jan;83(1):331–335. doi: 10.1172/JCI113879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boschcov P., Paiva A. C., Paiva T. B., Shimuta S. I. Further evidence for the existence of two receptor sites for bradykinin responsible for the diphasic effect in the rat isolated duodenum. Br J Pharmacol. 1984 Oct;83(2):591–600. doi: 10.1111/j.1476-5381.1984.tb16523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bouthillier J., Deblois D., Marceau F. Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. Br J Pharmacol. 1987 Oct;92(2):257–264. doi: 10.1111/j.1476-5381.1987.tb11319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cannon J. G., Clark B. D., Wingfield P., Schmeissner U., Losberger C., Dinarello C. A., Shaw A. R. Rabbit IL-1. Cloning, expression, biologic properties, and transcription during endotoxemia. J Immunol. 1989 Apr 1;142(7):2299–2306. [PubMed] [Google Scholar]
  5. Churchill L., Ward P. E. Relaxation of isolated mesenteric arteries by des-Arg9-bradykinin stimulation of B1 receptors. Eur J Pharmacol. 1986 Oct 14;130(1-2):11–18. doi: 10.1016/0014-2999(86)90178-0. [DOI] [PubMed] [Google Scholar]
  6. Couture R., Mizrahi J., Regoli D., Devroede G. Peptides and the human colon: an in vitro pharmacological study. Can J Physiol Pharmacol. 1981 Sep;59(9):957–964. doi: 10.1139/y81-146. [DOI] [PubMed] [Google Scholar]
  7. D'Orléans-Juste P., de Nucci G., Vane J. R. Kinins act on B1 or B2 receptors to release conjointly endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells. Br J Pharmacol. 1989 Apr;96(4):920–926. doi: 10.1111/j.1476-5381.1989.tb11903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deblois D., Bouthillier J., Marceau F. Effect of glucocorticoids, monokines and growth factors on the spontaneously developing responses of the rabbit isolated aorta to des-Arg9-bradykinin. Br J Pharmacol. 1988 Apr;93(4):969–977. doi: 10.1111/j.1476-5381.1988.tb11487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deblois D., Marceau F. The ability of des-Arg9-bradykinin to relax rabbit isolated mesenteric arteries is acquired during in vitro incubation. Eur J Pharmacol. 1987 Oct 6;142(1):141–144. doi: 10.1016/0014-2999(87)90664-9. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A., Cannon J. G., Mier J. W., Bernheim H. A., LoPreste G., Lynn D. L., Love R. N., Webb A. C., Auron P. E., Reuben R. C. Multiple biological activities of human recombinant interleukin 1. J Clin Invest. 1986 Jun;77(6):1734–1739. doi: 10.1172/JCI112495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dinarello C. A., Ikejima T., Warner S. J., Orencole S. F., Lonnemann G., Cannon J. G., Libby P. Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J Immunol. 1987 Sep 15;139(6):1902–1910. [PubMed] [Google Scholar]
  12. ELLIOTT D. F., HORTON E. W., LEWIS G. P. Actions of pure bradykinin. J Physiol. 1960 Oct;153:473–480. doi: 10.1113/jphysiol.1960.sp006548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. ERDOS E. G., SLOANE E. M. An enzyme in human blood plasma that inactivates bradykinin and kallidins. Biochem Pharmacol. 1962 Jul;11:585–592. doi: 10.1016/0006-2952(62)90119-3. [DOI] [PubMed] [Google Scholar]
  14. Förstermann U., Hertting G., Neufang B. The importance of endogenous prostaglandins other than prostacyclin, for the modulation of contractility of some rabbit blood vessels. Br J Pharmacol. 1984 Apr;81(4):623–630. doi: 10.1111/j.1476-5381.1984.tb16127.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Girardin E., Grau G. E., Dayer J. M., Roux-Lombard P., Lambert P. H. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med. 1988 Aug 18;319(7):397–400. doi: 10.1056/NEJM198808183190703. [DOI] [PubMed] [Google Scholar]
  16. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  17. Le J., Lin J. X., Henriksen-DeStefano D., Vilcek J. Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. J Immunol. 1986 Jun 15;136(12):4525–4530. [PubMed] [Google Scholar]
  18. Libby P., Ordovas J. M., Auger K. R., Robbins A. H., Birinyi L. K., Dinarello C. A. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol. 1986 Aug;124(2):179–185. [PMC free article] [PubMed] [Google Scholar]
  19. Libby P., Ordovas J. M., Birinyi L. K., Auger K. R., Dinarello C. A. Inducible interleukin-1 gene expression in human vascular smooth muscle cells. J Clin Invest. 1986 Dec;78(6):1432–1438. doi: 10.1172/JCI112732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Makino R., Hayashi K., Sugimura T. C-myc transcript is induced in rat liver at a very early stage of regeneration or by cycloheximide treatment. Nature. 1984 Aug 23;310(5979):697–698. doi: 10.1038/310697a0. [DOI] [PubMed] [Google Scholar]
  21. Marceau F., Lussier A., Regoli D., Giroud J. P. Pharmacology of kinins: their relevance to tissue injury and inflammation. Gen Pharmacol. 1983;14(2):209–229. doi: 10.1016/0306-3623(83)90001-0. [DOI] [PubMed] [Google Scholar]
  22. Marceau F., Tremblay B. Mitogenic effect of bradykinin and of des-Arg9-bradykinin on cultured fibroblasts. Life Sci. 1986 Dec 15;39(24):2351–2358. doi: 10.1016/0024-3205(86)90666-1. [DOI] [PubMed] [Google Scholar]
  23. Mason J. W., Kleeberg U., Dolan P., Colman R. W. Plasma kallikrein and Hageman factor in Gram-negative bacteremia. Ann Intern Med. 1970 Oct;73(4):545–551. doi: 10.7326/0003-4819-73-4-545. [DOI] [PubMed] [Google Scholar]
  24. McKenna T. M. Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility. Association with vascular cytokine release. J Clin Invest. 1990 Jul;86(1):160–168. doi: 10.1172/JCI114679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nwator I. A., Whalley E. T. Angiotensin converting enzyme inhibitors and expression of des-Arg9-BK (kinin B1) receptors in vivo. Eur J Pharmacol. 1989 Jan 24;160(1):125–132. doi: 10.1016/0014-2999(89)90661-4. [DOI] [PubMed] [Google Scholar]
  26. Proud D., Baumgarten C. R., Naclerio R. M., Ward P. E. Kinin metabolism in human nasal secretions during experimentally induced allergic rhinitis. J Immunol. 1987 Jan 15;138(2):428–434. [PubMed] [Google Scholar]
  27. Regoli D. C., Marceau F., Lavigne J. Induction of beta 1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide. Eur J Pharmacol. 1981 Apr 24;71(1):105–115. doi: 10.1016/0014-2999(81)90391-5. [DOI] [PubMed] [Google Scholar]
  28. Regoli D., Barabé J., Park W. K. Receptors for bradykinin in rabbit aortae. Can J Physiol Pharmacol. 1977 Aug;55(4):855–867. doi: 10.1139/y77-115. [DOI] [PubMed] [Google Scholar]
  29. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  30. Regoli D., Marceau F., Barabé J. De novo formation of vascular receptors for bradykinin. Can J Physiol Pharmacol. 1978 Aug;56(4):674–677. doi: 10.1139/y78-109. [DOI] [PubMed] [Google Scholar]
  31. Ringold G. M., Dieckmann B., Vannice J. L., Trahey M., McCormick F. Inhibition of protein synthesis stimulates the transcription of human beta-interferon genes in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3964–3968. doi: 10.1073/pnas.81.13.3964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sariban E., Luebbers R., Kufe D. Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes. Mol Cell Biol. 1988 Jan;8(1):340–346. doi: 10.1128/mcb.8.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  34. Verma I. M., Sassone-Corsi P. Proto-oncogene fos: complex but versatile regulation. Cell. 1987 Nov 20;51(4):513–514. doi: 10.1016/0092-8674(87)90115-2. [DOI] [PubMed] [Google Scholar]
  35. Warner S. J., Auger K. R., Libby P. Human interleukin 1 induces interleukin 1 gene expression in human vascular smooth muscle cells. J Exp Med. 1987 May 1;165(5):1316–1331. doi: 10.1084/jem.165.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Warner S. J., Libby P. Human vascular smooth muscle cells. Target for and source of tumor necrosis factor. J Immunol. 1989 Jan 1;142(1):100–109. [PubMed] [Google Scholar]
  37. Whalley E. T., Fritz H., Geiger R. Kinin receptors and angiotensin converting enzyme in rabbits basilar arteries. Naunyn Schmiedebergs Arch Pharmacol. 1983 Dec;324(4):296–301. doi: 10.1007/BF00502627. [DOI] [PubMed] [Google Scholar]
  38. Wilson D. D., de Garavilla L., Kuhn W., Togo J., Burch R. M., Steranka L. R. D-Arg-[Hyp3-D-Phe7]-bradykinin, a bradykinin antagonist, reduces mortality in a rat model of endotoxic shock. Circ Shock. 1989 Feb;27(2):93–101. [PubMed] [Google Scholar]
  39. deBlois D., Bouthillier J., Marceau F. Pharmacological modulation of the up-regulated responses to des-Arg9-bradykinin in vivo and in vitro. Immunopharmacology. 1989 May-Jun;17(3):187–198. doi: 10.1016/0162-3109(89)90047-7. [DOI] [PubMed] [Google Scholar]

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