Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 Oct;98(2):700–706. doi: 10.1111/j.1476-5381.1989.tb12645.x

Endothelium-dependent calcium-induced relaxation in the presence of Ca2+-antagonists in canine depolarized coronary arteries.

K Kikkawa 1, S Murata 1, T Nagao 1
PMCID: PMC1854722  PMID: 2819339

Abstract

1. We examined the mechanisms underlying Ca2+-induced relaxation in the presence of clentiazem, a new Ca2+-antagonist, in depolarized coronary arteries of the dog. 2. Ca2+ (3 x 10(-5)-3 x 10(-3) M) caused an unexpected relaxation in the presence of a high concentration of clentiazem (10(-6) M) in coronary, but not in mesenteric or renal arteries. 3. The Ca2+-induced relaxation was also observed in the presence of established Ca2+-antagonists such as diltiazem (3 x 10(-6) M), nifedipine (3 x 10(-8) M) and verapamil (3 x 10(-6) M). 4. The Ca2+-induced relaxation was inhibited by removal of the endothelium, treatment with oxyhaemoglobin (1.5 x 10(-6) M) or methylene blue (10(-5) M), but not by treatment with indomethacin (5 x 10(-6) M). 5. The Ca2+-induced relaxation was observed in an endothelium-denuded coronary artery segment when closely apposed to an endothelium-containing segment of coronary or mesenteric artery. 6. These results suggest that Ca2+-induced relaxation in the presence of high concentrations of Ca2+-antagonists is mediated through endothelium-derived relaxing factor (EDRF). In addition, Ca2+-antagonists do not affect the Ca2+-influx necessary for the release and/or synthesis of EDRF.

Full text

PDF
700

Images in this article

702Figure 1
on p.702

Selected References

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

  1. Feletou M., Vanhoutte P. M. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol. 1988 Mar;93(3):515–524. doi: 10.1111/j.1476-5381.1988.tb10306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  3. Griffith T. M., Edwards D. H., Lewis M. J., Henderson A. H. Evidence that cyclic guanosine monophosphate (cGMP) mediates endothelium-dependent relaxation. Eur J Pharmacol. 1985 Jun 7;112(2):195–202. doi: 10.1016/0014-2999(85)90496-0. [DOI] [PubMed] [Google Scholar]
  4. Ignarro L. J., Buga G. M., Wood K. S., Byrns R. E., Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265–9269. doi: 10.1073/pnas.84.24.9265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
  6. Jayakody R. L., Kappagoda C. T., Senaratne M. P., Sreeharan N. Absence of effect of calcium antagonists on endothelium-dependent relaxation in rabbit aorta. Br J Pharmacol. 1987 May;91(1):155–164. doi: 10.1111/j.1476-5381.1987.tb08994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kikkawa K., Murata S., Nagao T. Calcium antagonistic and spasmolytic activities of a new 1,5-benzothiazepine derivative in isolated canine and monkey arteries. Arzneimittelforschung. 1988 Apr;38(4):526–531. [PubMed] [Google Scholar]
  8. Komori K., Lorenz R. R., Vanhoutte P. M. Nitric oxide, ACh, and electrical and mechanical properties of canine arterial smooth muscle. Am J Physiol. 1988 Jul;255(1 Pt 2):H207–H212. doi: 10.1152/ajpheart.1988.255.1.H207. [DOI] [PubMed] [Google Scholar]
  9. Loeb A. L., Izzo N. J., Jr, Johnson R. M., Garrison J. C., Peach M. J. Endothelium-derived relaxing factor release associated with increased endothelial cell inositol trisphosphate and intracellular calcium. Am J Cardiol. 1988 Oct 5;62(11):36G–40G. doi: 10.1016/0002-9149(88)90030-6. [DOI] [PubMed] [Google Scholar]
  10. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation of rabbit aorta by certain ferrous hemoproteins. J Pharmacol Exp Ther. 1985 Jun;233(3):679–685. [PubMed] [Google Scholar]
  11. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  12. 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]
  13. Pfitzer G., Hofmann F., DiSalvo J., Rüegg J. C. cGMP and cAMP inhibit tension development in skinned coronary arteries. Pflugers Arch. 1984 Jul;401(3):277–280. doi: 10.1007/BF00582596. [DOI] [PubMed] [Google Scholar]
  14. Popescu L. M., Panoiu C., Hinescu M., Nutu O. The mechanism of cGMP-induced relaxation in vascular smooth muscle. Eur J Pharmacol. 1985 Jan 8;107(3):393–394. doi: 10.1016/0014-2999(85)90269-9. [DOI] [PubMed] [Google Scholar]
  15. Singer H. A., Peach M. J. Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. Hypertension. 1982 May-Jun;4(3 Pt 2):19–25. [PubMed] [Google Scholar]
  16. Tayo F. M., Bevan J. A. Extracellular calcium dependence of contraction and endothelium-dependent relaxation varies along the length of the aorta and its branches. J Pharmacol Exp Ther. 1987 Feb;240(2):594–601. [PubMed] [Google Scholar]

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

RESOURCES