Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Feb;105(2):279–284. doi: 10.1111/j.1476-5381.1992.tb14246.x

Endothelium-dependent and -independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery.

P Vuorinen 1, I Pörsti 1, T Metsä-Ketelä 1, V Manninen 1, H Vapaatalo 1, K E Laustiola 1
PMCID: PMC1908667  PMID: 1313722

Abstract

1. The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on vascular tone and cyclic nucleotide accumulation of noradrenaline-precontracted endothelium-intact and endothelium-denuded rat mesenteric artery rings were compared with the effects of the known purinoceptor agonists adenosine 5'-triphosphate (ATP) and adenosine. 2. GTP (10 microM-1 mM) dose-dependently relaxed endothelium-intact mesenteric artery rings by producing a rapid initial response followed by sustained relaxation resembling the relaxant response to acetylcholine. GTP also slightly relaxed endothelium-denuded artery rings. The acetylcholine- and GTP-induced relaxations of endothelium-intact rings were attenuated by NG-nitro L-arginine methyl ester (L-NAME, 330 microM) which attenuation was reversed with L-arginine (1 mM). 3. Guanosine (10 microM-1 mM) relaxed both endothelium-intact and -denuded artery rings in a dose-dependent manner. The relaxations were more pronounced in endothelium-intact preparations and were only slightly attenuated by L-NAME (330 microM). 4. ATP (1 microM-1 mM) and adenosine (10 microM-1 mM) dose-dependently relaxed endothelium-intact and -denuded artery rings. The responses were more pronounced in endothelium-intact vascular preparations. 5. GTP (100 microM) and guanosine (100 microM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in both endothelium-intact and -denuded artery rings corresponding to the relaxations observed. The concentrations of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were not affected. 6. ATP (100 microM) increased cyclic GMP concentration of endothelium-intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100 microM) and adenosine (100 microM) in endothelium-intact and -denuded vascular preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
282

Selected References

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

  1. Boeynaems J. M., Pearson J. D. P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms. Trends Pharmacol Sci. 1990 Jan;11(1):34–37. doi: 10.1016/0165-6147(90)90039-b. [DOI] [PubMed] [Google Scholar]
  2. Burnstock G., Kennedy C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol. 1985;16(5):433–440. doi: 10.1016/0306-3623(85)90001-1. [DOI] [PubMed] [Google Scholar]
  3. Coade S. B., Pearson J. D. Metabolism of adenine nucleotides in human blood. Circ Res. 1989 Sep;65(3):531–537. doi: 10.1161/01.res.65.3.531. [DOI] [PubMed] [Google Scholar]
  4. Collis M. G., Brown C. M. Adenosine relaxes the aorta by interacting with an A2 receptor and an intracellular site. Eur J Pharmacol. 1983 Dec 9;96(1-2):61–69. doi: 10.1016/0014-2999(83)90529-0. [DOI] [PubMed] [Google Scholar]
  5. De Mey J. G., Vanhoutte P. M. Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol. 1981 Jul;316:347–355. doi: 10.1113/jphysiol.1981.sp013792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Gaw A. J., Aberdeen J., Humphrey P. P., Wadsworth R. M., Burnstock G. Relaxation of sheep cerebral arteries by vasoactive intestinal polypeptide and neurogenic stimulation: inhibition by L-NG-monomethyl arginine in endothelium-denuded vessels. Br J Pharmacol. 1991 Mar;102(3):567–572. doi: 10.1111/j.1476-5381.1991.tb12213.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Geisbuhler T. P., Johnson D. A., Rovetto M. J. Cardiac myocyte guanosine transport and metabolism. Am J Physiol. 1987 Nov;253(5 Pt 1):C645–C651. doi: 10.1152/ajpcell.1987.253.5.C645. [DOI] [PubMed] [Google Scholar]
  10. Gordon J. L. Extracellular ATP: effects, sources and fate. Biochem J. 1986 Jan 15;233(2):309–319. doi: 10.1042/bj2330309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gordon J. L., Martin W. Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells. Br J Pharmacol. 1983 Jun;79(2):531–541. doi: 10.1111/j.1476-5381.1983.tb11028.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Houston D. A., Burnstock G., Vanhoutte P. M. Different P2-purinergic receptor subtypes of endothelium and smooth muscle in canine blood vessels. J Pharmacol Exp Ther. 1987 May;241(2):501–506. [PubMed] [Google Scholar]
  13. Ignarro L. J., Adams J. B., Horwitz P. M., Wood K. S. Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange. Comparison of heme-containing and heme-deficient enzyme forms. J Biol Chem. 1986 Apr 15;261(11):4997–5002. [PubMed] [Google Scholar]
  14. Ignarro L. J. Endothelium-derived nitric oxide: actions and properties. FASEB J. 1989 Jan;3(1):31–36. doi: 10.1096/fasebj.3.1.2642868. [DOI] [PubMed] [Google Scholar]
  15. Janssens P. M., De Jong C. C., Vink A. A., Van Haastert P. J. Regulatory properties of magnesium-dependent guanylate cyclase in Dictyostelium discoideum membranes. J Biol Chem. 1989 Mar 15;264(8):4329–4335. [PubMed] [Google Scholar]
  16. Kennedy C., Delbro D., Burnstock G. P2-purinoceptors mediate both vasodilation (via the endothelium) and vasoconstriction of the isolated rat femoral artery. Eur J Pharmacol. 1985 Jan 2;107(2):161–168. doi: 10.1016/0014-2999(85)90055-x. [DOI] [PubMed] [Google Scholar]
  17. Krishnamurthi S., Patel Y., Kakkar V. V. Inhibition of agonist-induced platelet aggregation, Ca2+ mobilization and granule secretion by guanosine 5'-[beta-thio]diphosphate and GDP in intact platelets. Evidence for an inhibitory mechanism unrelated to the inhibition of G-protein-GTP interaction. Biochem J. 1988 Feb 15;250(1):209–214. doi: 10.1042/bj2500209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kurose H., Ui M. Dual pathways of receptor-mediated cyclic GMP generation in NG108-15 cells as differentiated by susceptibility to islet-activating protein, pertussis toxin. Arch Biochem Biophys. 1985 May 1;238(2):424–434. doi: 10.1016/0003-9861(85)90183-3. [DOI] [PubMed] [Google Scholar]
  19. Kurtz A. Adenosine stimulates guanylate cyclase activity in vascular smooth muscle cells. J Biol Chem. 1987 May 5;262(13):6296–6300. [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. Laustiola K. E., Vuorinen P., Pörsti I., Metsä-Ketelä T., Manninen V., Vapaatalo H. Exogenous GTP enhances the effects of sodium nitrite on cyclic GMP accumulation, vascular smooth muscle relaxation and platelet aggregation. Pharmacol Toxicol. 1991 Jan;68(1):60–63. doi: 10.1111/j.1600-0773.1991.tb01209.x. [DOI] [PubMed] [Google Scholar]
  22. Lincoln T. M. Cyclic GMP and mechanisms of vasodilation. Pharmacol Ther. 1989;41(3):479–502. doi: 10.1016/0163-7258(89)90127-7. [DOI] [PubMed] [Google Scholar]
  23. Martin W., Cusack N. J., Carleton J. S., Gordon J. L. Specificity of P2-purinoceptor that mediates endothelium-dependent relaxation of the pig aorta. Eur J Pharmacol. 1985 Feb 5;108(3):295–299. doi: 10.1016/0014-2999(85)90452-2. [DOI] [PubMed] [Google Scholar]
  24. Moncada S., Palmer R. M., Higgs E. A. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989 Jun 1;38(11):1709–1715. doi: 10.1016/0006-2952(89)90403-6. [DOI] [PubMed] [Google Scholar]
  25. Moritoki H., Matsugi T., Takase H., Ueda H., Tanioka A. Evidence for the involvement of cyclic GMP in adenosine-induced, age-dependent vasodilatation. Br J Pharmacol. 1990 Jul;100(3):569–575. doi: 10.1111/j.1476-5381.1990.tb15848.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Needham L., Cusack N. J., Pearson J. D., Gordon J. L. Characteristics of the P2 purinoceptor that mediates prostacyclin production by pig aortic endothelial cells. Eur J Pharmacol. 1987 Feb 10;134(2):199–209. doi: 10.1016/0014-2999(87)90166-x. [DOI] [PubMed] [Google Scholar]
  28. Olsson R. A., Pearson J. D. Cardiovascular purinoceptors. Physiol Rev. 1990 Jul;70(3):761–845. doi: 10.1152/physrev.1990.70.3.761. [DOI] [PubMed] [Google Scholar]
  29. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Pearson J. D., Gordon J. L. Nucleotide metabolism by endothelium. Annu Rev Physiol. 1985;47:617–627. doi: 10.1146/annurev.ph.47.030185.003153. [DOI] [PubMed] [Google Scholar]
  32. Pearson J. D. Purine nucleotides as regulators of vessel tone. Biochem Soc Trans. 1988 Aug;16(4):480–482. doi: 10.1042/bst0160480. [DOI] [PubMed] [Google Scholar]
  33. Ramagopal M. V., Chitwood R. W., Jr, Mustafa S. J. Evidence for an A2 adenosine receptor in human coronary arteries. Eur J Pharmacol. 1988 Jul 14;151(3):483–486. doi: 10.1016/0014-2999(88)90548-1. [DOI] [PubMed] [Google Scholar]
  34. Rapoport R. M., Murad F. Endothelium-dependent and nitrovasodilator-induced relaxation of vascular smooth muscle: role of cyclic GMP. J Cyclic Nucleotide Protein Phosphor Res. 1983;9(4-5):281–296. [PubMed] [Google Scholar]
  35. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rose'Meyer R. B., Hope W. Evidence that A2 purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta. Br J Pharmacol. 1990 Jul;100(3):576–580. doi: 10.1111/j.1476-5381.1990.tb15849.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rubanyi G., Vanhoutte P. M. Endothelium-removal decreases relaxations of canine coronary arteries caused by beta-adrenergic agonists and adenosine. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):139–144. doi: 10.1097/00005344-198501000-00023. [DOI] [PubMed] [Google Scholar]
  38. Schini V. B., Junquero D. C., Scott-Burden T., Vanhoutte P. M. Interleukin-1 beta induces the production of an L-arginine-derived relaxing factor from cultured smooth muscle cells from rat aorta. Biochem Biophys Res Commun. 1991 Apr 15;176(1):114–121. doi: 10.1016/0006-291x(91)90897-g. [DOI] [PubMed] [Google Scholar]
  39. Tremblay J., Gerzer R., Hamet P. Cyclic GMP in cell function. Adv Second Messenger Phosphoprotein Res. 1988;22:319–383. [PubMed] [Google Scholar]
  40. Waldman S. A., Murad F. Cyclic GMP synthesis and function. Pharmacol Rev. 1987 Sep;39(3):163–196. [PubMed] [Google Scholar]
  41. Welford L. A., Cusack N. J., Hourani S. M. The structure-activity relationships of ectonucleotidases and of excitatory P2-purinoceptors: evidence that dephosphorylation of ATP analogues reduces pharmacological potency. Eur J Pharmacol. 1987 Sep 2;141(1):123–130. doi: 10.1016/0014-2999(87)90418-3. [DOI] [PubMed] [Google Scholar]
  42. White T. D., Angus J. A. Relaxant effects of ATP and adenosine on canine large and small coronary arteries in vitro. Eur J Pharmacol. 1987 Nov 3;143(1):119–126. doi: 10.1016/0014-2999(87)90741-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES