Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Dec;113(4):1131–1136. doi: 10.1111/j.1476-5381.1994.tb17114.x

Interactions of constitutive nitric oxide with PAF and thromboxane on rat intestinal vascular integrity in acute endotoxaemia.

F László 1, B J Whittle 1, S Moncada 1
PMCID: PMC1510527  PMID: 7889265

Abstract

1. The involvement of endogenous platelet activating factor (PAF) and thromboxane A2 in the acute microvascular damage in the ileum and colon induced by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) following endotoxin administration was investigated in the rat over a 1 h period. 2. Administration of L-NAME (1-10 mg kg-1, s.c.) concurrently with E. coli lipopolysaccharide (LPS; 3 mg kg-1, i.v.) dose-dependently increased vascular permeability in the ileum and colon, as determined by the leakage of radiolabelled albumin, and caused macroscopic mucosal damage in the ileum determined 1 h later. Neither LPS administration nor L-NAME (5 mg kg-1) alone affected resting vascular permeability. 3. Infusion of phenylephrine (10 micrograms kg-1 min-1, i.v. for 1 h) caused an elevation in blood pressure similar to that found following L-NAME administration (5 mg kg-1, i.v. or s.c.), but did not increase intestinal vascular permeability, when administered with LPS (3 mg kg-1, i.v.). 4. The increased vascular permeability in the ileum and colon and macroscopic damage in the ileum, induced by L-NAME (5 mg kg-1, s.c.) and LPS (3 mg kg-1, i.v.) was dose-dependently inhibited following s.c. pretreatment (15 min before challenge) with the thromboxane synthase inhibitors, OKY 1581 (5-25 mg kg-1) or 1-benzyl-imidazole (1-50 mg kg-1), or with the thromboxane receptor antagonist, BM 13177 (0.2-2 mg kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1134

Images in this article

1133Figure 1
on p.1133

Selected References

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

  1. Boughton-Smith N. K., Evans S. M., Laszlo F., Whittle B. J., Moncada S. The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Pharmacol. 1993 Nov;110(3):1189–1195. doi: 10.1111/j.1476-5381.1993.tb13940.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boughton-Smith N. K., Hutcheson I. R., Deakin A. M., Whittle B. J., Moncada S. Protective effect of S-nitroso-N-acetyl-penicillamine in endotoxin-induced acute intestinal damage in the rat. Eur J Pharmacol. 1990 Dec 4;191(3):485–488. doi: 10.1016/0014-2999(90)94185-z. [DOI] [PubMed] [Google Scholar]
  3. Boughton-Smith N. K., Hutcheson I., Whittle B. J. Relationship between PAF-acether and thromboxane A2 biosynthesis in endotoxin-induced intestinal damage in the rat. Prostaglandins. 1989 Sep;38(3):319–333. doi: 10.1016/0090-6980(89)90136-6. [DOI] [PubMed] [Google Scholar]
  4. Casals-Stenzel J. Protective effect of WEB 2086, a novel antagonist of platelet activating factor, in endotoxin shock. Eur J Pharmacol. 1987 Mar 17;135(2):117–122. doi: 10.1016/0014-2999(87)90602-9. [DOI] [PubMed] [Google Scholar]
  5. Filep J. G., Földes-Filep E. Modulation by nitric oxide of platelet-activating factor-induced albumin extravasation in the conscious rat. Br J Pharmacol. 1993 Dec;110(4):1347–1352. doi: 10.1111/j.1476-5381.1993.tb13967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Halushka P. V., Cook J. A., Wise W. C. Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat. Br J Clin Pharmacol. 1983;15 (Suppl 1):133S–139S. doi: 10.1111/j.1365-2125.1983.tb02124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamid-Bloomfield S., Whittle B. J. Antagonism of PGD2 vasodepressor responses in the rat in vivo by the novel, selective antagonist, BW A868C. Br J Pharmacol. 1989 Feb;96(2):307–312. doi: 10.1111/j.1476-5381.1989.tb11818.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harlan J. M., Harker L. A., Reidy M. A., Gajdusek C. M., Schwartz S. M., Striker G. E. Lipopolysaccharide-mediated bovine endothelial cell injury in vitro. Lab Invest. 1983 Mar;48(3):269–274. [PubMed] [Google Scholar]
  9. Hutcheson I. R., Whittle B. J., Boughton-Smith N. K. Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol. 1990 Dec;101(4):815–820. doi: 10.1111/j.1476-5381.1990.tb14163.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koltai M., Hosford D., Guinot P., Esanu A., Braquet P. PAF. A review of its effects, antagonists and possible future clinical implications (Part II). Drugs. 1991 Aug;42(2):174–204. doi: 10.2165/00003495-199142020-00002. [DOI] [PubMed] [Google Scholar]
  11. Koltai M., Hosford D., Guinot P., Esanu A., Braquet P. Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I). Drugs. 1991 Jul;42(1):9–29. doi: 10.2165/00003495-199142010-00002. [DOI] [PubMed] [Google Scholar]
  12. Kubes P., Granger D. N. Nitric oxide modulates microvascular permeability. Am J Physiol. 1992 Feb;262(2 Pt 2):H611–H615. doi: 10.1152/ajpheart.1992.262.2.H611. [DOI] [PubMed] [Google Scholar]
  13. Kubes P., Suzuki M., Granger D. N. Modulation of PAF-induced leukocyte adherence and increased microvascular permeability. Am J Physiol. 1990 Nov;259(5 Pt 1):G859–G864. doi: 10.1152/ajpgi.1990.259.5.G859. [DOI] [PubMed] [Google Scholar]
  14. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laszlo F., Whittle B. J., Moncada S. Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors. Br J Pharmacol. 1994 Apr;111(4):1309–1315. doi: 10.1111/j.1476-5381.1994.tb14887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Martinez-Cuesta M. A., Barrachina M. D., Piqué J. M., Whittle B. J., Esplugues J. V. The role of nitric oxide and platelet-activating factor in the inhibition by endotoxin of pentagastrin-stimulated gastric acid secretion. Eur J Pharmacol. 1992 Aug 6;218(2-3):351–354. doi: 10.1016/0014-2999(92)90191-6. [DOI] [PubMed] [Google Scholar]
  17. Meyrick B. O., Ryan U. S., Brigham K. L. Direct effects of E coli endotoxin on structure and permeability of pulmonary endothelial monolayers and the endothelial layer of intimal explants. Am J Pathol. 1986 Jan;122(1):140–151. [PMC free article] [PubMed] [Google Scholar]
  18. Olanoff L. S., Cook J. A., Eller T., Knapp D. R., Halushka P. V. Protective effects of trans-13-APT, a thromboxane receptor antagonist, in endotoxemia. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):114–120. doi: 10.1097/00005344-198501000-00019. [DOI] [PubMed] [Google Scholar]
  19. Radomski M. W., Palmer R. M., Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987 Nov 7;2(8567):1057–1058. doi: 10.1016/s0140-6736(87)91481-4. [DOI] [PubMed] [Google Scholar]
  20. Radomski M. W., Palmer R. M., Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1987 Nov;92(3):639–646. doi: 10.1111/j.1476-5381.1987.tb11367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosam A. C., Wallace J. L., Whittle B. J. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature. 1986 Jan 2;319(6048):54–56. doi: 10.1038/319054a0. [DOI] [PubMed] [Google Scholar]
  22. Salter M., Knowles R. G., Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett. 1991 Oct 7;291(1):145–149. doi: 10.1016/0014-5793(91)81123-p. [DOI] [PubMed] [Google Scholar]
  23. Wallace J. L., Steel G., Whittle B. J., Lagente V., Vargaftig B. Evidence for platelet-activating factor as a mediator of endotoxin-induced gastrointestinal damage in the rat. Effects of three platelet-activating factor antagonists. Gastroenterology. 1987 Oct;93(4):765–773. doi: 10.1016/0016-5085(87)90438-0. [DOI] [PubMed] [Google Scholar]
  24. Wallace J. L., Whittle B. J. Picomole doses of platelet-activating factor predispose the gastric mucosa to damage by topical irritants. Prostaglandins. 1986 May;31(5):989–998. doi: 10.1016/0090-6980(86)90028-6. [DOI] [PubMed] [Google Scholar]
  25. Whittle B. J., Boughton-Smith N. K., Hutcheson I. R., Esplugues J. V., Wallace J. L. Increased intestinal formation of Paf in endotoxin-induced damage in the rat. Br J Pharmacol. 1987 Sep;92(1):3–4. doi: 10.1111/j.1476-5381.1987.tb11287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Whittle B. J., Lopez-Belmonte J., Moncada S. Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol. 1990 Mar;99(3):607–611. doi: 10.1111/j.1476-5381.1990.tb12977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Whittle B. J., Morishita T., Ohya Y., Leung F. W., Guth P. H. Microvascular actions of platelet-activating factor on rat gastric mucosa and submucosa. Am J Physiol. 1986 Dec;251(6 Pt 1):G772–G778. doi: 10.1152/ajpgi.1986.251.6.G772. [DOI] [PubMed] [Google Scholar]

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

RESOURCES