Influence of experimental diabetes on regulatory mechanisms of vascular response of rabbit carotid artery to acetylcholine

The purpose of this study was to analyse the influence of experimental diabetes on vascular response of rabbit carotid artery to acetylcholine (Ach). We compared the Ach-induced relaxant response of isolated arterial segments obtained from both control and diabetic animals. To assess the influence of the endothelium, this cell layer was mechanically removed in some of the arterial segments ("rubbed arteries") from each experimental group. Ach induced a concentration-related endothelium-mediated relaxation of carotid artery from control rabbits that was significantly higher with respect to that obtained in diabetic animals. Pretreatment with N-G-nitro-L-arginine (L-NA) induced a concentration-dependent inhibition of relaxant response to Ach, which was significantly higher in carotid arteries isolated from diabetic rabbits. Incubation of rubbed arteries with L-NA almost abolished the relaxant response to Ach in arterial segments from both control and diabetic animals. Indomethacin potentiated Ach-induced response of carotid arteries from control rabbits, without modifying that obtained in those from diabetic animals. Aminoguanidine did not significantly inhibit the relaxant action of Ach in arterial segments from either control or diabetic rabbits. These results suggest that diabetes impairs endothelial modulatory mechanisms of vascular response of rabbit carotid artery to Ach. This endothelial dysfunction is neither related with a lower release of nitric oxide (NO) or prostacyclin. Diabetes impairs the production of some arachidonic acid vasoconstrictor derivative. There has been observed an increased modulatory activity of NO, but this is not related with the expression of an inducible isoform of NO synthase.