0494 : Vascular protective effects of an amphiphilic nitrone against hyperglycemia-induced oxidative damages

Abstract

Overconsumption of sugary drinks and food has recently been implicated in the pathogenesis of cardiovascular disease. Indeed, during acute hyperglycemia, increased oxidative stress has been proposed as a key trigger of vascular dysfunction. Nitrones are well known spin traps of noxious free radicals, and therefore can act as antioxidants but exhibit NO-donor properties as well. Several series of amphiphilic nitrones, i.e. water-soluble and lipophilic at the same time, were developed with the expectation that amphiphilicity may favor intracellular localization. Consequently, our objective was to investigate the protective effect of an amphiphilic nitrone (LPBNAH) on oxidative stress impairments of vascular function following an acute hyperglycemia. In order to evaluate this hypothesis, we removed aortas from Wistar rats (n=20). Aortic rings (2-3mm) were mounted in an organ chamber between two wire hooks which were connected to a force transducer (EMKA, France) to record changes in isometric force. Endothelial vasodilatory function in response to acetylcholine (ACh, 10 -10 to 10 -4 M) was evaluated in normoglycemic (11mM) and hyperglycemic (100mM) conditions in presence or not of LPBNAH (100μM) as well as other antioxidants such as N-acetylcysteine (NAC, 10μM) or Apocynin (10μM). We observed in our study an impairment of endothelial function associated with an increased reactive oxygen species production (evaluated by EPR) in hyperglycemic conditions. Interestingly, these damages were completely reversed by both NAC and apocynin, thus confirming the well-known pro-oxidant effect of hyperglycemia. Regarding the effect of our amphiphilic nitrone, we observed a major protective effect on endothelial hyperglycemic impairments. Indeed, in presence of LPBNAH, maximal vasodilatation and ACh sensitivity were preserved from hyperglycemic impairments. Our results points out the biological protective effect of such molecule in a pro-oxidant condition such as hyperglycemia. The author hereby declares no conflict of interest