Abstract
Incubation of vascular endothelial cells with S.typhosa endotoxin and interferon-gamma caused a time- and concentration-dependent reduction in the viability of the cells. The cytotoxic effect was inhibited in a concentration-dependent manner by NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, and by the glucocorticoids dexamethasone and hydrocortisone, two inhibitors of the induction of NO synthase. These findings indicate that in these cells the cytotoxic effect of endotoxin is mediated by the NO synthesized by an inducible NO synthase. This induction of NO synthase in vascular endothelial cells may represent a mechanism of local endothelial damage during endotoxin shock and other immunologically based conditions.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blackwell G. J., Radomski M., Vargas J. R., Moncada S. Prostacyclin prolongs viability of washed human platelets. Biochim Biophys Acta. 1982 Sep 17;718(1):60–65. doi: 10.1016/0304-4165(82)90009-5. [DOI] [PubMed] [Google Scholar]
- Gryglewski R. J., Moncada S., Palmer R. M. Bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) from porcine aortic endothelial cells. Br J Pharmacol. 1986 Apr;87(4):685–694. doi: 10.1111/j.1476-5381.1986.tb14586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hecker M., Sessa W. C., Harris H. J., Anggård E. E., Vane J. R. The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8612–8616. doi: 10.1073/pnas.87.21.8612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
- Masferrer J. L., Zweifel B. S., Seibert K., Needleman P. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest. 1990 Oct;86(4):1375–1379. doi: 10.1172/JCI114850. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- O'Connor K. J., Moncada S. Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells. Biochim Biophys Acta. 1991 Oct 21;1097(3):227–231. doi: 10.1016/0925-4439(91)90040-g. [DOI] [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10043–10047. doi: 10.1073/pnas.87.24.10043. [DOI] [PMC free article] [PubMed] [Google Scholar]