Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Sep;107(1):196–201. doi: 10.1111/j.1476-5381.1992.tb14486.x

Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic aorta.

H Moritoki 1, T Hisayama 1, S Takeuchi 1, H Miyano 1, W Kondoh 1
PMCID: PMC1907606  PMID: 1358382

Abstract

1. The mechanism of the vasorelaxant effect of platelet activating factor (PAF) on rat thoracic aorta and the effect of aging on the PAF-induced relaxation were investigated. 2. PAF at concentrations causing relaxation induced marked increases in guanosine 3':5'-cyclic monophosphate (cyclic GMP) production, but did not induce an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP). 3. Removal of the endothelium by mechanical rubbing, and treatment with the PAF antagonists CV-3988, CV-6209 and FR-900452, the nitric oxide biosynthesis inhibitor, NG-nitro L-arginine, the radical scavenger, haemoglobin, and the soluble guanylate cyclase inhibitor, methylene blue, inhibited PAF-induced relaxation and abolished or attenuated PAF-stimulated cyclic GMP production. 4. The relaxation was greatest in arteries from rats aged 4 weeks. With an increase in age, the response of the arteries to PAF was attenuated. 5. Endothelium-dependent cyclic GMP production also decreased with increase in age of the rats. 6. These results suggest that PAF stimulates production of nitric oxide from L-arginine by acting on the PAF receptors in the endothelium, which in turn stimulates soluble guanylate cyclase in the smooth muscle cells, and so increases production of cyclic GMP, thus relaxing the arteries. Age-associated decrease in PAF-induced relaxation may result from a reduction of cyclic GMP formation.

Full text

PDF
196

Selected References

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

  1. Benveniste J. Platelet-activating factor, a new mediator of anaphylaxis and immune complex deposition from rabbit and human basophils. Nature. 1974 Jun 7;249(457):581–582. doi: 10.1038/249581a0. [DOI] [PubMed] [Google Scholar]
  2. Cabot M. C., Blank M. L., Welsh C. J., Horan M. J., Cress E. A., Snyder F. Metabolism of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine by cell cultures. Life Sci. 1982 Dec 20;31(25):2891–2898. doi: 10.1016/0024-3205(82)90680-4. [DOI] [PubMed] [Google Scholar]
  3. Cervoni P., Herzlinger H. E., Lai F. M., Tanikella T. K. Aortic vascular and atrial responses to (+/-)-1-O-octadecyl-2-acetyl-glyceryl-3-phosphorylcholine. Br J Pharmacol. 1983 Jul;79(3):667–671. doi: 10.1111/j.1476-5381.1983.tb10003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chiba Y., Mikoda N., Kawasaki H., Ito K. Endothelium-dependent relaxant action of platelet activating factor in the rat mesenteric artery. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):68–73. doi: 10.1007/BF00195060. [DOI] [PubMed] [Google Scholar]
  5. Chu K. M., Gerber J. G., Nies A. S. Local vasodilator effect of platelet activating factor in the gastric, mesenteric and femoral arteries of the dog. J Pharmacol Exp Ther. 1988 Sep;246(3):996–1000. [PubMed] [Google Scholar]
  6. D'Humières S., Russo-Marie F., Vargaftig B. B. PAF-acether-induced synthesis of prostacyclin by human endothelial cells. Eur J Pharmacol. 1986 Nov 12;131(1):13–19. doi: 10.1016/0014-2999(86)90510-8. [DOI] [PubMed] [Google Scholar]
  7. Evans T. W., Chung K. F., Rogers D. F., Barnes P. J. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl Physiol (1985) 1987 Aug;63(2):479–484. doi: 10.1152/jappl.1987.63.2.479. [DOI] [PubMed] [Google Scholar]
  8. Gerkens J. F. Reproducible vasodilatation by platelet-activating factor in blood- and Krebs-perfused rat kidneys is albumin-dependent. Eur J Pharmacol. 1990 Feb 27;177(3):119–126. doi: 10.1016/0014-2999(90)90261-4. [DOI] [PubMed] [Google Scholar]
  9. Gruetter C. A., Kadowitz P. J., Ignarro L. J. Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite. Can J Physiol Pharmacol. 1981 Feb;59(2):150–156. doi: 10.1139/y81-025. [DOI] [PubMed] [Google Scholar]
  10. Honma M., Satoh T., Takezawa J., Ui M. An ultrasensitive method for the simultaneous determination of cyclic AMP and cyclic GMP in small-volume samples from blood and tissue. Biochem Med. 1977 Dec;18(3):257–273. doi: 10.1016/0006-2944(77)90060-6. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Kamata K., Mori T., Shigenobu K., Kasuya Y. Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels. Br J Pharmacol. 1989 Dec;98(4):1360–1364. doi: 10.1111/j.1476-5381.1989.tb12685.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kamitani T., Katamoto M., Tatsumi M., Katsuta K., Ono T., Kikuchi H., Kumada S. Mechanism(s) of the hypotensive effect of synthetic 1-O-octadecyl-2-O-acetyl-glycero-3-phosphorylcholine. Eur J Pharmacol. 1984 Mar 2;98(3-4):357–366. doi: 10.1016/0014-2999(84)90284-x. [DOI] [PubMed] [Google Scholar]
  14. Kasuya Y., Masuda Y., Shigenobu K. Possible role of endothelium in the vasodilator response of rat thoracic aorta to platelet activating factor (PAF). J Pharmacobiodyn. 1984 Feb;7(2):138–142. doi: 10.1248/bpb1978.7.138. [DOI] [PubMed] [Google Scholar]
  15. Kobayashi Y., Hattori K. Nitroarginine inhibits endothelium-derived relaxation. Jpn J Pharmacol. 1990 Jan;52(1):167–169. doi: 10.1254/jjp.52.167. [DOI] [PubMed] [Google Scholar]
  16. Lai F. M., Shepherd C. A., Cervoni P., Wissner A. Hypotensive and vasodilatory activity of (+/-) 1-o-octadecyl-2-acetyl glyceryl-3-phosphorylcholine in the normotensive rat. Life Sci. 1983 Mar 7;32(10):1159–1166. doi: 10.1016/0024-3205(83)90122-4. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Moritoki H., Hosoki E., Ishida Y. Age-related decrease in endothelium-dependent dilator response to histamine in rat mesenteric artery. Eur J Pharmacol. 1986 Jul 15;126(1-2):61–67. doi: 10.1016/0014-2999(86)90738-7. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Moritoki H., Tanioka A., Maeshiba Y., Iwamoto T., Ishida Y., Araki H. Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation. Br J Pharmacol. 1988 Dec;95(4):1015–1022. doi: 10.1111/j.1476-5381.1988.tb11734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moritoki H., Yoshikawa T., Hisayama T., Takeuchi S. Possible mechanisms of age-associated reduction of vascular relaxation caused by atrial natriuretic peptide. Eur J Pharmacol. 1992 Jan 7;210(1):61–68. doi: 10.1016/0014-2999(92)90652-k. [DOI] [PubMed] [Google Scholar]
  22. Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  23. Okamoto M., Yoshida K., Nishikawa M., Hayashi K., Uchida I., Kohsaka M., Aoki H. Studies of platelet activating factor (PAF) antagonists from microbial products. III. Pharmacological studies of FR-900452 in animal models. Chem Pharm Bull (Tokyo) 1986 Jul;34(7):3005–3010. doi: 10.1248/cpb.34.3005. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Rapoport R. M., Waldman S. A., Schwartz K., Winquist R. J., Murad F. Effects of atrial natriuretic factor, sodium nitroprusside, and acetylcholine on cyclic GMP levels and relaxation in rat aorta. Eur J Pharmacol. 1985 Sep 24;115(2-3):219–229. doi: 10.1016/0014-2999(85)90694-6. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Shigenobu K., Masuda Y., Tanaka Y., Kasuya Y. Platelet activating factor analogues: lack of correlation between their activities to produce hypotension and endothelium-mediated vasodilation. J Pharmacobiodyn. 1985 Feb;8(2):128–133. doi: 10.1248/bpb1978.8.128. [DOI] [PubMed] [Google Scholar]
  28. Shigenobu K., Tanaka Y., Maeda T., Kasuya Y. Potentiation by bovine serum albumin (BSA) of endothelium-dependent vasodilator response to acetyl glyceryl ether phosphorylcholine (AGEPC). J Pharmacobiodyn. 1987 May;10(5):220–228. doi: 10.1248/bpb1978.10.220. [DOI] [PubMed] [Google Scholar]
  29. Tanaka S., Kasuya Y., Masuda Y., Shigenobu K. Studies on the hypotensive effects of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) in rats, guinea pigs, rabbits, and dogs. J Pharmacobiodyn. 1983 Nov;6(11):866–873. doi: 10.1248/bpb1978.6.866. [DOI] [PubMed] [Google Scholar]
  30. Terashita Z., Imura Y., Takatani M., Tsushima S., Nishikawa K. CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo. J Pharmacol Exp Ther. 1987 Jul;242(1):263–268. [PubMed] [Google Scholar]
  31. Terashita Z., Tsushima S., Yoshioka Y., Nomura H., Inada Y., Nishikawa K. CV-3988 - a specific antagonist of platelet activating factor (PAF). Life Sci. 1983 Apr 25;32(17):1975–1982. doi: 10.1016/0024-3205(83)90049-8. [DOI] [PubMed] [Google Scholar]
  32. Ueda H., Moritoki H. Possible association of decrease of ATP-induced vascular relaxation with reduction of cyclic GMP during aging. Arch Int Pharmacodyn Ther. 1991 Mar-Apr;310:35–45. [PubMed] [Google Scholar]
  33. Vanhoutte P. M., Houston D. S. Platelets, endothelium, and vasospasm. Circulation. 1985 Oct;72(4):728–734. doi: 10.1161/01.cir.72.4.728. [DOI] [PubMed] [Google Scholar]
  34. Voelkel N. F., Chang S. W., Pfeffer K. D., Worthen S. G., McMurtry I. F., Henson P. M. PAF antagonists: different effects on platelets, neutrophils, guinea pig ileum and PAF-induced vasodilation in isolated rat lung. Prostaglandins. 1986 Sep;32(3):359–372. doi: 10.1016/0090-6980(86)90005-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES