Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Dec;113(4):1548–1553. doi: 10.1111/j.1476-5381.1994.tb17172.x

Display of the characteristics of endothelium-derived hyperpolarizing factor by a cytochrome P450-derived arachidonic acid metabolite in the coronary microcirculation.

J Bauersachs 1, M Hecker 1, R Busse 1
PMCID: PMC1510544  PMID: 7889312

Abstract

1. In addition to nitric oxide (NO) and prostacyclin (PGI2) an endothelium-derived factor, which hyperpolarizes vascular smooth muscle cells via activation of K+ channels, contributes to the dilator effect of bradykinin in different vascular beds. Since this so-called endothelium-derived hyperpolarizing factor (EDHF) also seems to play an important role in the coronary circulation, we investigated its nature and mechanism of action in the rat isolated perfused heart (Langendorff preparation). 2. Bolus injections of bradykinin (1, 10, and 100 pmol) elicited a transient dose-dependent dilator response (e.g., 12 +/- 2% decrease in coronary perfusion pressure (CPP) at 10 pmol bradykinin, n = 41). Administration of the cyclo-oxygenase inhibitor, diclofenac (1 microM), augmented the bradykinin-induced dilation approximately twofold (n = 9 P < 0.01). Combined treatment with the NO synthase inhibitor, NG-nitro-L-arginine (30 microM) and diclofenac (1 microM) significantly reduced the duration, but increased the amplitude of the dilator response to bradykinin (27 +/- 2% decrease in CPP, n = 24, P < 0.01). 3. The abolition of this NG-nitro-L-arginine/diclofenac-insensitive dilator response to bradykinin by tetrabutylammonium (0.3 mM), an inhibitor of Ca(2+)-dependent K+ channels (4 +/- 1% decrease in CPP, n = 6, P < 0.01), supports the view that the dilator compound released in the coronary microcirculation is EDHF. 4. This EDHF-type dilation was reversibly inhibited by the phospholipase A2 inhibitor, quinacrine (3 microM, 9 +/- 3% decrease in CPP, n = 6, P < 0.01) and by the cytochrome P450 inhibitor SKF525a (3 microM, 6 +/- 1% decrease in CPP, n = 6, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1548

Selected References

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

  1. 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]
  2. Blatz A. L., Magleby K. L. Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle. Nature. 1986 Oct 23;323(6090):718–720. doi: 10.1038/323718a0. [DOI] [PubMed] [Google Scholar]
  3. Bény J. L., Pacicca C. Bidirectional electrical communication between smooth muscle and endothelial cells in the pig coronary artery. Am J Physiol. 1994 Apr;266(4 Pt 2):H1465–H1472. doi: 10.1152/ajpheart.1994.266.4.H1465. [DOI] [PubMed] [Google Scholar]
  4. Chen G., Yamamoto Y., Miwa K., Suzuki H. Hyperpolarization of arterial smooth muscle induced by endothelial humoral substances. Am J Physiol. 1991 Jun;260(6 Pt 2):H1888–H1892. doi: 10.1152/ajpheart.1991.260.6.H1888. [DOI] [PubMed] [Google Scholar]
  5. Cowan C. L., Cohen R. A. Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and -independent responses. Am J Physiol. 1991 Sep;261(3 Pt 2):H830–H835. doi: 10.1152/ajpheart.1991.261.3.H830. [DOI] [PubMed] [Google Scholar]
  6. Hecker M., Bara A. T., Busse R. Relaxation of isolated coronary arteries by angiotensin-converting enzyme inhibitors: role of endothelium-derived kinins. J Vasc Res. 1993 Sep-Oct;30(5):257–262. doi: 10.1159/000159004. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Hu S., Kim H. S. Activation of K+ channel in vascular smooth muscles by cytochrome P450 metabolites of arachidonic acid. Eur J Pharmacol. 1993 Jan 12;230(2):215–221. doi: 10.1016/0014-2999(93)90805-r. [DOI] [PubMed] [Google Scholar]
  10. Kauser K., Rubanyi G. M. Bradykinin-induced, N omega-nitro-L-arginine-insensitive endothelium-dependent relaxation of porcine coronary arteries is not mediated by bioassayable relaxing substances. J Cardiovasc Pharmacol. 1992;20 (Suppl 12):S101–S104. doi: 10.1097/00005344-199204002-00029. [DOI] [PubMed] [Google Scholar]
  11. Lamontagne D., König A., Bassenge E., Busse R. Prostacyclin and nitric oxide contribute to the vasodilator action of acetylcholine and bradykinin in the intact rabbit coronary bed. J Cardiovasc Pharmacol. 1992 Oct;20(4):652–657. doi: 10.1097/00005344-199210000-00020. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Myers P. R., Guerra R., Jr, Harrison D. G. Release of multiple endothelium-derived relaxing factors from porcine coronary arteries. J Cardiovasc Pharmacol. 1992 Sep;20(3):392–400. doi: 10.1097/00005344-199209000-00008. [DOI] [PubMed] [Google Scholar]
  14. Nagao T., Vanhoutte P. M. Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. J Physiol. 1992 Jan;445:355–367. doi: 10.1113/jphysiol.1992.sp018928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakashima M., Mombouli J. V., Taylor A. A., Vanhoutte P. M. Endothelium-dependent hyperpolarization caused by bradykinin in human coronary arteries. J Clin Invest. 1993 Dec;92(6):2867–2871. doi: 10.1172/JCI116907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Richard V., Tanner F. C., Tschudi M., Lüscher T. F. Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. Am J Physiol. 1990 Nov;259(5 Pt 2):H1433–H1439. doi: 10.1152/ajpheart.1990.259.5.H1433. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Suzuki H., Chen G., Yamamoto Y. Endothelium-derived hyperpolarizing factor (EDHF). Jpn Circ J. 1992 Feb;56(2):170–174. doi: 10.1253/jcj.56.170. [DOI] [PubMed] [Google Scholar]

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

RESOURCES