The effect of clonidine, an alpha-2 adrenergic receptor agonist, on inflammatory response and postischemic endothelium function during early reperfusion in healthy volunteers

Maximilien Gourdin, Philippe Dubois, Francois Mullier, Bernard Chatelain, Jean-Michel Dogné, Baudouin Marchandise, Jacques Jamart, Marc De Kock

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

Ischemia-reperfusion disturbs endothelial physiology and generates a proinflammatory state. Animal studies showed that clonidine administered prior hypoxia improves posthypoxic endothelial function. To investigate this effect in human, we have assessed the postischemic endothelium function and the proinflammatory state in healthy volunteers with and without clonidine. Seven volunteers were included. Each subject underwent the experimental protocol (15 minutes nondominant forearm ischemia) with and without clonidine. Endothelial function was assessed by flow-mediated dilatation (FMD) in the brachial artery before ischemia (FMDPI), immediately after ischemia (FMDIAI), and 15 minutes after ischemia (FMD15AI). Neutrophil (CD11b/CD18) and platelet (CD42b) activations were measured by flow cytometry during reperfusion in blood samples from ischemic (local) and nonischemic (systemic) forearms. Proinflammatory state was assessed by serum concentration of interleukin (IL)-1β and -6. Clonidine does not influence baseline FMD (P = 0.118) but improves FMDIAI (P = 0.018) and FMD15AI (P = 0.018). It increases platelet activation in systemic circulation (P = 0.003) during reperfusion but not in local circulation (P = 0.086). Clonidine increases neutrophil activation in local circulation (P = 0.001) but not in systemic circulation (P = 0.642). In local circulation, clonidine decreases IL-6 (P = 0.044) but does not influence IL-1β (P = 0.113). By contrast, it decreases both IL-6 (P = 0.026) and IL-1β (P = 0.027) concentrations in systemic circulation. In conclusion, clonidine improves endothelial function and modulates inflammation during reperfusion.
langue originaleAnglais
Pages (de - à)553-60
Nombre de pages8
journalJournal of cardiovascular pharmacology
Volume60
Numéro de publication6
Les DOIs
Etat de la publicationPublié - déc. 2012

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