| Autor: |
Gosgnach, Willy, Boixel, Cristophe, Névo, Nathalie, Poiraud, Thierry, Michel, JeanBaptiste |
| Zdroj: |
Journal of Cardiovascular Pharmacology; August 2001, Vol. 38 Issue: 2 p191-199, 9p |
| Abstrakt: |
Nebivolol is a highly selective 1adrenoreceptorblocking agent with a peculiar pharmacodynamic profile. It has peripheral acute vasodilating properties that are mediated by modulation of the endogenous production of nitric oxide. In this study we analyzed the different signaling pathways implicated in the response of human umbilical vein endothelial cells to nebivolol. Its effect on endothelial transduction pathways was determined by assaying phospholipase C and A2activities and cyclic adenosine monophosphate AMP production. Variations in intracellular calcium concentration were also measured. Our results showed that nebivolol activates a calciumindependent transduction pathway that implicates an increase in adenylate cyclase and phospholipase A2 activity. 1or 2Adrenoreceptor antagonists do not inhibit the action of nebivolol. However, its action on cyclic AMP production is inhibited by bupranolol, a 13adrenoreceptor antagonist, and Scyanopindolol, a selective 3adrenoreceptor antagonist. Nebivolol also dosedependently increased nitrite production. This effect was inhibited by bupranolol, suggesting that the possible action of nebivolol on 3adrenoreceptor is involved in its vasodilating properties. This study suggests that nebivolol could behave as a 3adrenoreceptor agonist and induce some calciumindependent pathways implicating phospholipase A2and adenylate cyclase. This agonistic activity of nebivolol seems to be responsible for its endotheliumdependent vasodilating activity. |
| Databáze: |
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