The effects of clonidine on the posthypoxic vasomotricity : from animal experimentations to the clinical trial
(2012)
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- Authors
- Supervisors
- De Kock, Marc
- Abstract
- (en) Physician is daily confronted with ischemia-reperfusion and its consequences. Reperfusion of an ischemic organ is essential for its viability but induces endothelial and vascular dysfunctions that jeopardize the posthypoxic organ recovery. Alpha2-adrenergic receptor agonists (A2RA) improve posthypoxic function of several organs in animal models and humans. However, mechanisms underlying this protective effect are not fully understood. If central effects of A2RA are often proposed to explain it, recent in vitro studies show similar findings, demonstrating a local beneficial effect of A2RA in hypoxia-reoxygenation (H-R). Blood vessels and endothelium are particularly exposed to H-R and constitute an interesting target to study the A2RA protective effects. In this thesis, author presents the results of several studies investigating the effects of the clonidine, an A2RA available in medicine, on the posthypoxic vasomotricity on in vitro animal models and healthy volunteers. Prehypoxic clonidine administration improves posthypoxic endothelium-dependent dilatation (PED) and contractility (PC) on young rat aorta. These effects are mediated by 2A- and 2B- and/or 2C-adrenergic receptors. The activation of nitric oxide synthase and cyclooxygenase play a pivotal role. By cons, clonidine decreases PED and does not influence PC on old rat aorta. On old rat pretreated by simvastatin, an inhibitor of HMG-Coenzyme A reductase, clonidine improved PED. Finally, the last study carried out on healthy volunteers is closer to clinical situations met daily. We show that oral administration of 150 micrograms clonidine improves endothelial function of the brachial artery of upper limb subjected to an ischemia. In addition, concentrations of interleukin-1β and -6 during the early reperfusion were significantly lower when the volunteers took clonidine. By cons, its positive effects could be to counteract by the greater concomitant platelet and neutrophil activations.
- Affiliations
Citations
Gourdin, M. (2012). The effects of clonidine on the posthypoxic vasomotricity : from animal experimentations to the clinical trial. https://hdl.handle.net/2078.5/161664