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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Oct;107(2):382–386. doi: 10.1111/j.1476-5381.1992.tb12755.x

Calmodulin antagonists inhibit endothelium-dependent hyperpolarization in the canine coronary artery.

T Nagao 1, S Illiano 1, P M Vanhoutte 1
PMCID: PMC1907875  PMID: 1422587

Abstract

1. The effects of the calmodulin antagonists, calmidazolium and fendiline were investigated on endothelium-dependent hyperpolarization in the canine coronary artery. The membrane potential of vascular smooth muscle cells was measured with the microelectrode technique. 2. Smooth muscle cells of the canine coronary artery had a resting membrane potential of -50 mV. Bradykinin and the Ca(2+)-ionophore, A23187, induced concentration- and endothelium-dependent hyperpolarization. The hyperpolarization induced by a supramaximal concentration of bradykinin (10(-6) M) reached approximately 20 mV. 3. Calmidazolium (10(-5) M) and fendiline (10(-4) M) inhibited hyperpolarization induced by bradykinin and A23187. By contrast, calmidazolium did not affect the hyperpolarization induced by lemakalim, an opener of ATP-sensitive K(+)-channels. 4. These observations suggest that calmodulin is involved in the generation of endothelium-dependent membrane hyperpolarization of vascular smooth muscle.

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Selected References

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  1. Ahlijanian M. K., Cooper D. M. Antagonism of calmodulin-stimulated adenylate cyclase by trifluoperazine, calmidazolium and W-7 in rat cerebellar membranes. J Pharmacol Exp Ther. 1987 May;241(2):407–414. [PubMed] [Google Scholar]
  2. Boulanger C., Hendrickson H., Lorenz R. R., Vanhoutte P. M. Release of different relaxing factors by cultured porcine endothelial cells. Circ Res. 1989 Jun;64(6):1070–1078. doi: 10.1161/01.res.64.6.1070. [DOI] [PubMed] [Google Scholar]
  3. Brayden J. E. Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation. Am J Physiol. 1990 Sep;259(3 Pt 2):H668–H673. doi: 10.1152/ajpheart.1990.259.3.H668. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Busse R., Lückhoff A., Winter I., Mülsch A., Pohl U. Fendiline and calmidazolium enhance the release of endothelium-derived relaxant factor and of prostacyclin from cultured endothelial cells. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):79–84. doi: 10.1007/BF00169481. [DOI] [PubMed] [Google Scholar]
  6. Busse R., Mülsch A. Calcium-dependent nitric oxide synthesis in endothelial cytosol is mediated by calmodulin. FEBS Lett. 1990 Jun 4;265(1-2):133–136. doi: 10.1016/0014-5793(90)80902-u. [DOI] [PubMed] [Google Scholar]
  7. Bény J. L., Brunet P. C. Neither nitric oxide nor nitroglycerin accounts for all the characteristics of endothelially mediated vasodilatation of pig coronary arteries. Blood Vessels. 1988;25(6):308–311. [PubMed] [Google Scholar]
  8. Chen G. F., Suzuki H. Calcium dependency of the endothelium-dependent hyperpolarization in smooth muscle cells of the rabbit carotid artery. J Physiol. 1990 Feb;421:521–534. doi: 10.1113/jphysiol.1990.sp017959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen G., Suzuki H., Weston A. H. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988 Dec;95(4):1165–1174. doi: 10.1111/j.1476-5381.1988.tb11752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Cheung W. Y. Calmodulin plays a pivotal role in cellular regulation. Science. 1980 Jan 4;207(4426):19–27. doi: 10.1126/science.6243188. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Fleming I., Gray G. A., Schott C., Stoclet J. C. Inducible but not constitutive production of nitric oxide by vascular smooth muscle cells. Eur J Pharmacol. 1991 Aug 6;200(2-3):375–376. doi: 10.1016/0014-2999(91)90602-m. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Förstermann U., Pollock J. S., Schmidt H. H., Heller M., Murad F. Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1788–1792. doi: 10.1073/pnas.88.5.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gietzen K. Comparison of the calmodulin antagonists compound 48/80 and calmidazolium. Biochem J. 1983 Dec 15;216(3):611–616. doi: 10.1042/bj2160611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoeffner U., Feletou M., Flavahan N. A., Vanhoutte P. M. Canine arteries release two different endothelium-derived relaxing factors. Am J Physiol. 1989 Jul;257(1 Pt 2):H330–H333. doi: 10.1152/ajpheart.1989.257.1.H330. [DOI] [PubMed] [Google Scholar]
  18. Ignarro L. J., Byrns R. E., Buga G. M., Wood K. S. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987 Dec;61(6):866–879. doi: 10.1161/01.res.61.6.866. [DOI] [PubMed] [Google Scholar]
  19. Illiano S., Nagao T., Vanhoutte P. M. Calmidazolium, a calmodulin inhibitor, inhibits endothelium-dependent relaxations resistant to nitro-L-arginine in the canine coronary artery. Br J Pharmacol. 1992 Oct;107(2):387–392. doi: 10.1111/j.1476-5381.1992.tb12756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson J. D., Wittenauer L. A. A fluorescent calmodulin that reports the binding of hydrophobic inhibitory ligands. Biochem J. 1983 May 1;211(2):473–479. doi: 10.1042/bj2110473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kamm K. E., Stull J. T. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol. 1985;25:593–620. doi: 10.1146/annurev.pa.25.040185.003113. [DOI] [PubMed] [Google Scholar]
  22. Kihira M., Matsuzawa K., Tokuno H., Tomita T. Effects of calmodulin antagonists on calcium-activated potassium channels in pregnant rat myometrium. Br J Pharmacol. 1990 Jun;100(2):353–359. doi: 10.1111/j.1476-5381.1990.tb15808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Nagao T., Vanhoutte P. M. Hyperpolarization contributes to endothelium-dependent relaxations to acetylcholine in femoral veins of rats. Am J Physiol. 1991 Oct;261(4 Pt 2):H1034–H1037. doi: 10.1152/ajpheart.1991.261.4.H1034. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  28. Stoclet J. C., Gérard D., Kilhoffer M. C., Lugnier C., Miller R., Schaeffer P. Calmodulin and its role in intracellular calcium regulation. Prog Neurobiol. 1987;29(4):321–364. doi: 10.1016/0301-0082(87)90018-9. [DOI] [PubMed] [Google Scholar]
  29. Van de Voorde J., Vanheel B., Leusen I. Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. Circ Res. 1992 Jan;70(1):1–8. doi: 10.1161/01.res.70.1.1. [DOI] [PubMed] [Google Scholar]
  30. Weinheimer G., Osswald H. Inhibition of endothelium-dependent smooth muscle relaxation by calmodulin antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1986 Apr;332(4):391–397. doi: 10.1007/BF00500093. [DOI] [PubMed] [Google Scholar]
  31. Weir S. W., Weston A. H. The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels. Br J Pharmacol. 1986 May;88(1):121–128. doi: 10.1111/j.1476-5381.1986.tb09478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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