Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Nov;116(5):2473–2481. doi: 10.1111/j.1476-5381.1995.tb15098.x

Endothelium-dependent relaxations mediated by inducible B1 and constitutive B2 kinin receptors in the bovine isolated coronary artery.

G R Drummond 1, T M Cocks 1
PMCID: PMC1909050  PMID: 8581287

Abstract

1. Rings of bovine left anterior descending coronary artery (LAD) were contracted with the thromboxane A2-mimetic, U46619 (1-30 nM), to approximately 40% of their maximum contraction to 125 mM KCl Krebs solution (KPSSmax) for comparison of responses to the B1 and B2 kinin receptor agonists, des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK), respectively. Relaxation responses were normalized as percentages of the initial U46619-induced contraction level, while contractile responses were expressed as percentages of KPSSmax. 2. After 6 h of in vitro incubation in Krebs solution at 37 degrees C, des-Arg9-BK (pEC50, 8.00 +/- 0.08; maximum response (Rmax), 93.9 +/- 1.9%) and BK (pEC50, 9.75 +/- 0.07; Rmax, 100.1 +/- 0.7%) caused endothelium-dependent relaxations in precontracted rings of bovine LAD which were competitively and selectively antagonized by the B1 receptor antagonist, des-Arg9-[Leu8]-BK (pA2, 6.27 +/- 0.11) and the B2 receptor antagonist Hoc-140 (pA2, 9.63 +/- 0.14), respectively. 3. At 3 h of in vitro incubation, the sensitivity (pEC50, 7.45 +/- 0.10) and Rmax (84.6 +/- 3.3%) to des-Arg9-BK were significantly less than those obtained in the same tissues at 6 h (pEC50, 7.94 +/- 0.06; Rmax, 91.4 +/- 2.5%), whereas endothelium-dependent relaxations to BK and ACh were unaffected by incubation time. 4. Relaxation responses to des-ARg9-BK, but not BK, at both 3 h and 6 h were significantly attenuated by the protein synthesis inhibitors, cycloheximide (30 and 100 microM) and actinomycin D (2 microM). 5. At 6 h, the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NOARG, 100 microM), caused a significant 2 fold decrease in pEC50 (9.58 +/- 0.03) but had no effect on Rmax for BK. For des-Arg9-BK, L-NOARG (100 microM) caused a marked and significant decrease in both the pEC50 and Rmax and revealed contractions to low concentrations of des-Arg9-BK. In both cases, L-NOARG inhibition was reversed in the presence of L-arginine (10 mM). 6. At 6 h removal of the endothelium abolished relaxation responses to des-Arg9-BK and BK, and for des-Arg9-BK, but not BK, unmasked concentration-dependent contractions (pEC50, 7.57 +/- 0.09; Rmax, 83.4 +/- 9.1%). The sensitivity of contractions to des-Arg9-BK increased slightly from 3 h (pEC50, 7.37 +/- 0.08) to 6 h (pEC50, 7.62 +/- 0.12) of in vitro incubation; however, there was a small but significant depression in the maximum response over this time (Rmax, 126.8 +/- 8.5% and 103.3 +/- 8.6% for 3 h and 6 h of incubation respectively). 7. In conclusion, the bovine LAD contains inducible B1 and constitutive B2 endothelial cell kinin receptors, both of which mediate endothelium-dependent relaxation partly via the release of NO. B1 receptors were also present on the smooth muscle layer of the bovine LAD.

Full text

PDF
2473

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. Auch-Schwelk W., Bossaller C., Claus M., Graf K., Gräfe M., Fleck E. ACE inhibitors are endothelium dependent vasodilators of coronary arteries during submaximal stimulation with bradykinin. Cardiovasc Res. 1993 Feb;27(2):312–317. doi: 10.1093/cvr/27.2.312. [DOI] [PubMed] [Google Scholar]
  3. Barabé J., Babiuk C., Regoli D. Binding of [3H]des-Arg9-BK to rabbit anterior mesenteric vein. Can J Physiol Pharmacol. 1982 Dec;60(12):1551–1555. doi: 10.1139/y82-229. [DOI] [PubMed] [Google Scholar]
  4. Baydoun A. R., Woodward B. Effects of bradykinin in the rat isolated perfused heart: role of kinin receptors and endothelium-derived relaxing factor. Br J Pharmacol. 1991 Jul;103(3):1829–1833. doi: 10.1111/j.1476-5381.1991.tb09871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beny J. L., Brunet P., Huggel H. Interaction of bradykinin and des-Arg9-bradykinin with isolated pig coronary arteries: mechanical and electrophysiological events. Regul Pept. 1987 Apr;17(4):181–190. doi: 10.1016/0167-0115(87)90061-9. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cherry P. D., Furchgott R. F., Zawadzki J. V., Jothianandan D. Role of endothelial cells in relaxation of isolated arteries by bradykinin. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2106–2110. doi: 10.1073/pnas.79.6.2106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cowan C. L., Palacino J. J., Najibi S., Cohen R. A. Potassium channel-mediated relaxation to acetylcholine in rabbit arteries. J Pharmacol Exp Ther. 1993 Sep;266(3):1482–1489. [PubMed] [Google Scholar]
  9. D'Orléans-Juste P., Dion S., Mizrahi J., Regoli D. Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium. Eur J Pharmacol. 1985 Aug 7;114(1):9–21. doi: 10.1016/0014-2999(85)90515-1. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Eggerickx D., Raspe E., Bertrand D., Vassart G., Parmentier M. Molecular cloning, functional expression and pharmacological characterization of a human bradykinin B2 receptor gene. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1306–1313. doi: 10.1016/0006-291x(92)90445-q. [DOI] [PubMed] [Google Scholar]
  13. Galizzi J. P., Bodinier M. C., Chapelain B., Ly S. M., Coussy L., Giraud S., Neliat G., Jean T. Up-regulation of [3H]-des-Arg10-kallidin binding to the bradykinin B1 receptor by interleukin-1 beta in isolated smooth muscle cells: correlation with B1 agonist-induced PGI2 production. Br J Pharmacol. 1994 Oct;113(2):389–394. doi: 10.1111/j.1476-5381.1994.tb17001.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garland C. J., Plane F., Kemp B. K., Cocks T. M. Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci. 1995 Jan;16(1):23–30. doi: 10.1016/s0165-6147(00)88969-5. [DOI] [PubMed] [Google Scholar]
  15. Hess J. F., Borkowski J. A., Macneil T., Stonesifer G. Y., Fraher J., Strader C. D., Ransom R. W. Differential pharmacology of cloned human and mouse B2 bradykinin receptors. Mol Pharmacol. 1994 Jan;45(1):1–8. [PubMed] [Google Scholar]
  16. Hock F. J., Wirth K., Albus U., Linz W., Gerhards H. J., Wiemer G., Henke S., Breipohl G., König W., Knolle J. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991 Mar;102(3):769–773. doi: 10.1111/j.1476-5381.1991.tb12248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holzmann S., Kukovetz W. R., Windischhofer W., Paschke E., Graier W. F. Pharmacologic differentiation between endothelium-dependent relaxations sensitive and resistant to nitro-L-arginine in coronary arteries. J Cardiovasc Pharmacol. 1994 May;23(5):747–756. doi: 10.1097/00005344-199405000-00009. [DOI] [PubMed] [Google Scholar]
  18. Kilpatrick E. V., Cocks T. M. Evidence for differential roles of nitric oxide (NO) and hyperpolarization in endothelium-dependent relaxation of pig isolated coronary artery. Br J Pharmacol. 1994 Jun;112(2):557–565. doi: 10.1111/j.1476-5381.1994.tb13110.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Martin G. R., Bolofo M. L., Giles H. Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence. Br J Pharmacol. 1992 Mar;105(3):643–652. doi: 10.1111/j.1476-5381.1992.tb09033.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McEachern A. E., Shelton E. R., Bhakta S., Obernolte R., Bach C., Zuppan P., Fujisaki J., Aldrich R. W., Jarnagin K. Expression cloning of a rat B2 bradykinin receptor. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7724–7728. doi: 10.1073/pnas.88.17.7724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Menke J. G., Borkowski J. A., Bierilo K. K., MacNeil T., Derrick A. W., Schneck K. A., Ransom R. W., Strader C. D., Linemeyer D. L., Hess J. F. Expression cloning of a human B1 bradykinin receptor. J Biol Chem. 1994 Aug 26;269(34):21583–21586. [PubMed] [Google Scholar]
  22. Mombouli J. V., Illiano S., Nagao T., Scott-Burden T., Vanhoutte P. M. Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. Circ Res. 1992 Jul;71(1):137–144. doi: 10.1161/01.res.71.1.137. [DOI] [PubMed] [Google Scholar]
  23. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  24. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nagao T., Vanhoutte P. M. Endothelium-derived hyperpolarizing factor and endothelium-dependent relaxations. Am J Respir Cell Mol Biol. 1993 Jan;8(1):1–6. doi: 10.1165/ajrcmb/8.1.1. [DOI] [PubMed] [Google Scholar]
  26. Pinto A., Abraham N. G., Mullane K. M. Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: contribution of a cytochrome P-450-dependent pathway. J Pharmacol Exp Ther. 1987 Mar;240(3):856–863. [PubMed] [Google Scholar]
  27. Pruneau D., Bélichard P. Induction of bradykinin B1 receptor-mediated relaxation in the isolated rabbit carotid artery. Eur J Pharmacol. 1993 Aug 3;239(1-3):63–67. doi: 10.1016/0014-2999(93)90976-o. [DOI] [PubMed] [Google Scholar]
  28. Pruneau D., Luccarini J. M., Robert C., Bélichard P. Induction of kinin B1 receptor-dependent vasoconstriction following balloon catheter injury to the rabbit carotid artery. Br J Pharmacol. 1994 Apr;111(4):1029–1034. doi: 10.1111/j.1476-5381.1994.tb14847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  31. Regoli D., Drapeau G., Rovero P., Dion S., D'Orléans-Juste P., Barabé J. The actions of kinin antagonists on B1 and B2 receptor systems. Eur J Pharmacol. 1986 Apr 9;123(1):61–65. doi: 10.1016/0014-2999(86)90687-4. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Regoli D., Mizrahi J., D'Orléans-Juste P., Caranikas S. Effects of kinins on isolated blood vessels. Role of endothelium. Can J Physiol Pharmacol. 1982 Dec;60(12):1580–1583. doi: 10.1139/y82-234. [DOI] [PubMed] [Google Scholar]
  34. Rosolowsky M., Campbell W. B. Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid. Am J Physiol. 1993 Feb;264(2 Pt 2):H327–H335. doi: 10.1152/ajpheart.1993.264.2.H327. [DOI] [PubMed] [Google Scholar]
  35. Schneck K. A., Hess J. F., Stonesifer G. Y., Ransom R. W. Bradykinin B1 receptors in rabbit aorta smooth muscle cells in culture. Eur J Pharmacol. 1994 Feb 15;266(3):277–282. doi: 10.1016/0922-4106(94)90137-6. [DOI] [PubMed] [Google Scholar]
  36. Staszewska-Woolley J., Woodman O. L. Kinin receptors mediating the effects of bradykinin on the coronary circulation in anaesthetized greyhounds. Eur J Pharmacol. 1991 Apr 10;196(1):9–14. doi: 10.1016/0014-2999(91)90402-c. [DOI] [PubMed] [Google Scholar]
  37. Stork A. P., Cocks T. M. Pharmacological reactivity of human epicardial coronary arteries: characterization of relaxation responses to endothelium-derived relaxing factor. Br J Pharmacol. 1994 Dec;113(4):1099–1104. doi: 10.1111/j.1476-5381.1994.tb17109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Toda N., Bian K., Akiba T., Okamura T. Heterogeneity in mechanisms of bradykinin action in canine isolated blood vessels. Eur J Pharmacol. 1987 Mar 31;135(3):321–329. doi: 10.1016/0014-2999(87)90681-9. [DOI] [PubMed] [Google Scholar]
  39. Whalley E. T., Amure Y. O., Lye R. H. Analysis of the mechanism of action of bradykinin on human basilar artery in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):433–437. doi: 10.1007/BF00165559. [DOI] [PubMed] [Google Scholar]
  40. Wiemer G., Wirth K. Production of cyclic GMP via activation of B1 and B2 kinin receptors in cultured bovine aortic endothelial cells. J Pharmacol Exp Ther. 1992 Aug;262(2):729–733. [PubMed] [Google Scholar]
  41. 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]

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

RESOURCES