Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Mar;102(3):759–763. doi: 10.1111/j.1476-5381.1991.tb12246.x

The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit.

G R May 1, P Crook 1, P K Moore 1, C P Page 1
PMCID: PMC1917930  PMID: 1364849

Abstract

1. Intravenous (i.v.) administration of adenosine diphosphate (ADP), platelet activating factor (PAF) and thrombin induced a dose-related accumulation of 111indium-labelled platelets within the thoracic region of anaesthetized rabbits. 2. I.v. administration of the inhibitor of NO biosynthesis, L-NG-nitro arginine methyl ester (L-NAME; 10 mg kg-1) significantly potentiated the peak platelet accumulation induced by ADP, PAF and thrombin. Additionally L-NAME prolonged the disaggregation of platelets in comparison to D-NAME (10 mg kg-1). Such changes were reversible by the administration of L-arginine (900 mg kg-1). 3. I.v. administration of PAF induced a small accumulation of 111indium-labelled neutrophils within the pulmonary circulation which could be greatly potentiated by pretreatment of the animals with L-NAME. In contrast, thrombin administration did not cause significant accumulation of 11indium-labelled erythrocytes in the pulmonary circulation of anaesthetized rabbits. 4. Intracarotid (i.c.) administration of thrombin induced a marked accumulation of radiolabelled platelets within the cranial vasculature which was not potentiated by the prior administration of L-NAME (at either 10 mg kg-1 or 100 mg kg-1). 5. These results suggest that endogenous NO may regulate platelet and polymorphonuclear leukocyte activation within the pulmonary but not the cerebral circulation of rabbits.

Full text

PDF

Selected References

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

  1. Azuma H., Ishikawa M., Sekizaki S. Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol. 1986 Jun;88(2):411–415. doi: 10.1111/j.1476-5381.1986.tb10218.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bhardwaj R., Page C. P., May G. R., Moore P. K. Endothelium-derived relaxing factor inhibits platelet aggregation in human whole blood in vitro and in the rat in vivo. Eur J Pharmacol. 1988 Nov 15;157(1):83–91. doi: 10.1016/0014-2999(88)90474-8. [DOI] [PubMed] [Google Scholar]
  3. Boje K. M., Fung H. L. Endothelial nitric oxide generating enzyme(s) in the bovine aorta: subcellular location and metabolic characterization. J Pharmacol Exp Ther. 1990 Apr;253(1):20–26. [PubMed] [Google Scholar]
  4. Chester A. H., O'Neil G. S., Moncada S., Tadjkarimi S., Yacoub M. H. Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. Lancet. 1990 Oct 13;336(8720):897–900. doi: 10.1016/0140-6736(90)92269-n. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gibson A., Mirzazadeh S., Hobbs A. J., Moore P. K. L-NG-monomethyl arginine and L-NG-nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcygeus muscle. Br J Pharmacol. 1990 Mar;99(3):602–606. doi: 10.1111/j.1476-5381.1990.tb12976.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hogan J. C., Lewis M. J., Henderson A. H. In vivo EDRF activity influences platelet function. Br J Pharmacol. 1988 Aug;94(4):1020–1022. doi: 10.1111/j.1476-5381.1988.tb11616.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Knowles R. G., Palacios M., Palmer R. M., Moncada S. Kinetic characteristics of nitric oxide synthase from rat brain. Biochem J. 1990 Jul 1;269(1):207–210. doi: 10.1042/bj2690207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Loskutoff D. J., Edgington T. E. Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3903–3907. doi: 10.1073/pnas.74.9.3903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. May G. R., Herd C. M., Butler K. D., Page C. P. Radioisotopic model for investigating thromboembolism in the rabbit. J Pharmacol Methods. 1990 Aug;24(1):19–35. doi: 10.1016/0160-5402(90)90046-n. [DOI] [PubMed] [Google Scholar]
  11. McCall T. B., Boughton-Smith N. K., Palmer R. M., Whittle B. J., Moncada S. Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J. 1989 Jul 1;261(1):293–296. doi: 10.1042/bj2610293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  13. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Page C. P., Paul W., Morley J. An in vivo model for studying platelet aggregation and disaggregation. Thromb Haemost. 1982 Jun 28;47(3):210–213. [PubMed] [Google Scholar]
  15. Radomski M. W., Palmer R. M., Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5193–5197. doi: 10.1073/pnas.87.13.5193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Rosenblum W. I., Nelson G. H., Povlishock J. T. Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse. Circ Res. 1987 Feb;60(2):169–176. doi: 10.1161/01.res.60.2.169. [DOI] [PubMed] [Google Scholar]
  18. Salvemini D., de Nucci G., Gryglewski R. J., Vane J. R. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6328–6332. doi: 10.1073/pnas.86.16.6328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tayeh M. A., Marletta M. A. Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J Biol Chem. 1989 Nov 25;264(33):19654–19658. [PubMed] [Google Scholar]
  20. Thiemermann C., May G. R., Page C. P., Vane J. R. Endothelin-1 inhibits platelet aggregation in vivo: a study with 111indium-labelled platelets. Br J Pharmacol. 1990 Feb;99(2):303–308. doi: 10.1111/j.1476-5381.1990.tb14699.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES