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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Sep;92(1):237–240. doi: 10.1111/j.1476-5381.1987.tb11317.x

Selective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery.

U Alheid 1, C Dudel 1, U Förstermann 1
PMCID: PMC1853611  PMID: 2444300

Abstract

1 Acetylcholine, substance P, prostaglandin E1 and the nitrovasodilator glyceryl trinitrate induced concentration-dependent relaxations of endothelium-intact strips of rabbit coeliac artery precontracted with noradrenaline. 2 Endothelium-denuded strip preparations contracted to acetylcholine and showed no response to substance P. The relaxant response to prostaglandin E1 was unimpaired after removal of endothelium, whereas the response to glyceryl trinitrate was increased. 3 A 20 min exposure of endothelium-intact strips to gossypol, an irreversible inhibitor of the production and/or release of endothelium-derived relaxing factor, abolished vasodilatation in response to the endothelium-dependent agents acetylcholine and substance P, did not change relaxations to prostaglandin E1, but significantly enhanced relaxations in response to glyceryl trinitrate. 4 In view of the assumed common mechanism of action of endothelium-derived relaxing factor and nitrovasodilators, these results suggest an interference of the two active principles at the level of the vascular smooth muscle cell.

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Selected References

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  1. Böhme E., Grossmann G., Herz J., Mülsch A., Spies C., Schultz G. Regulation of cyclic GMP formation by soluble guanylate cyclase: stimulation by NO-containing compounds. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:259–266. [PubMed] [Google Scholar]
  2. Furchgott R. F. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. doi: 10.1146/annurev.pa.24.040184.001135. [DOI] [PubMed] [Google Scholar]
  3. Förstermann U., Goppelt-Strübe M., Frölich J. C., Busse R. Inhibitors of acyl-coenzyme A:lysolecithin acyltransferase activate the production of endothelium-derived vascular relaxing factor. J Pharmacol Exp Ther. 1986 Jul;238(1):352–359. [PubMed] [Google Scholar]
  4. Förstermann U., Mülsch A., Böhme E., Busse R. Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries. Circ Res. 1986 Apr;58(4):531–538. doi: 10.1161/01.res.58.4.531. [DOI] [PubMed] [Google Scholar]
  5. Förstermann U. Properties and mechanisms of production and action of endothelium-derived relaxing factor. J Cardiovasc Pharmacol. 1986;8 (Suppl 10):S45–S51. doi: 10.1097/00005344-198600101-00010. [DOI] [PubMed] [Google Scholar]
  6. Förstermann U., Trogisch G., Busse R. Species-dependent differences in the nature of endothelium-derived vascular relaxing factor. Eur J Pharmacol. 1984 Nov 27;106(3):639–643. doi: 10.1016/0014-2999(84)90071-2. [DOI] [PubMed] [Google Scholar]
  7. Griffith T. M., Edwards D. H., Lewis M. J., Newby A. C., Henderson A. H. The nature of endothelium-derived vascular relaxant factor. Nature. 1984 Apr 12;308(5960):645–647. doi: 10.1038/308645a0. [DOI] [PubMed] [Google Scholar]
  8. Hamasaki Y., Tai H. H. Gossypol, a potent inhibitor of arachidonate 5- and 12-lipoxygenases. Biochim Biophys Acta. 1985 Mar 27;834(1):37–41. doi: 10.1016/0005-2760(85)90173-0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Murad F. Cyclic guanosine monophosphate as a mediator of vasodilation. J Clin Invest. 1986 Jul;78(1):1–5. doi: 10.1172/JCI112536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. POOLE J. C., SANDERS A. G., FLOREY H. W. The regeneration of aortic endothelium. J Pathol Bacteriol. 1958 Jan;75(1):133–143. doi: 10.1002/path.1700750116. [DOI] [PubMed] [Google Scholar]
  12. Peach M. J., Singer H. A., Loeb A. L. Mechanisms of endothelium-dependent vascular smooth muscle relaxation. Biochem Pharmacol. 1985 Jun 1;34(11):1867–1874. doi: 10.1016/0006-2952(85)90300-4. [DOI] [PubMed] [Google Scholar]
  13. Rapoport R. M., Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res. 1983 Mar;52(3):352–357. doi: 10.1161/01.res.52.3.352. [DOI] [PubMed] [Google Scholar]
  14. Shirasaki Y., Su C. Endothelium removal augments vasodilation by sodium nitroprusside and sodium nitrite. Eur J Pharmacol. 1985 Aug 7;114(1):93–96. doi: 10.1016/0014-2999(85)90527-8. [DOI] [PubMed] [Google Scholar]
  15. Shirasaki Y., Su C., Lee T. J., Kolm P., Cline W. H., Jr, Nickols G. A. Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension. J Pharmacol Exp Ther. 1986 Dec;239(3):861–866. [PubMed] [Google Scholar]
  16. Vegesna R. V., Diamond J. Effects of prostaglandin E1, isoproterenol and forskolin on cyclic AMP levels and tension in rabbit aortic rings. Life Sci. 1986 Jul 28;39(4):303–311. doi: 10.1016/0024-3205(86)90648-x. [DOI] [PubMed] [Google Scholar]
  17. White D. G., Lewis M. J., Griffith T. M., Edwards D. H., Henderson A. H. Influence of endothelium on drug-induced relaxation of the rabbit aorta. Eur J Pharmacol. 1986 Feb 11;121(1):19–23. doi: 10.1016/0014-2999(86)90387-0. [DOI] [PubMed] [Google Scholar]

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