Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level
Article first published online: 2 FEB 2009
2002 British Pharmacological Society
British Journal of Pharmacology
Volume 135, Issue 5, pages 1175–1182, March 2002
How to Cite
Jiang, J.-L., Li, N.-s., Li, Y.-J. and Deng, H.-W. (2002), Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. British Journal of Pharmacology, 135: 1175–1182. doi: 10.1038/sj.bjp.0704563
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- (Received October 16, 2001, Revised December 12, 2001, Accepted December 13, 2001)
- Asymmetric dimethylarginine;
- low-density lipoprotein;
- nitric oxide
Oxide low-density lipoprotein (ox-LDL) is believed to play an important role in early events of atherogenesis, and asymmetric dimethylarginine (ADMA) is associated with the development of endothelial dysfunction. The present study examined the effect of a single injection of native low-density lipoprotein (LDL) on endothelium function and the serum level of ADMA and the effect of probucol on endothelium function and ADMA level in rats.
Endothelial injury was induced by intravenous injection of LDL at the dose of 2, 4, or 6 mg kg−1 for 24, 48, or 72 h, and vasodilator responses to acetylcholine in the aortic rings and serum levels of ADMA, nitrite/nitrate (NO) and malondialdehyde (MDA) were determined.
Pretreatment with LDL markedly reduced endothelium-dependent relaxation in a concentration-dependent manner. Inhibition of vasodilator responses to acetylcholine by LDL was abolished in the presence of L-arginine (3×10−4 M). Serum levels of ADMA and MDA were significantly elevated in the rats pretreated with LDL, while serum level of nitrite/nitrate was markedly decreased.
Pretreatment with probucol significantly improved endothelium-dependent relaxation, decreased concentrations of ADMA and MDA and increased nitrite/nitrate level in the rats treated with LDL. A similar effect was seen in the rats pretreated with an antioxidant vitamin E.
These results suggest that a single injection of native LDL causes endothelial dysfunction by elevation of ADMA levels and that the protective effect of probucol on endothelial cells is related to reduction of ADMA concentration.
British Journal of Pharmacology (2002) 135, 1175–1182; doi:10.1038/sj.bjp.0704563