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 diab etes 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 o f the endothelium, this cell layer was mechanically removed in some of the arterial segments ("rubbed arteries") from each experimental group. Ach ind uced a concentration-related endothelium-mediated relaxation of carotid art ery 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 relax ant response to Ach in arterial segments from both control and diabetic ani mals. Indomethacin potentiated Ach-induced response of carotid arteries fro m control rabbits, without modifying that obtained in those from diabetic a nimals. Aminoguanidine did not significantly inhibit the relaxant action of Ach in arterial segments from either control or diabetic rabbits. These re sults suggest that diabetes impairs endothelial modulatory mechanisms of va scular response of rabbit carotid artery to Ach. This endothelial dysfuncti on is neither related with a lower release of nitric oxide (NO) or prostacy clin. Diabetes impairs the production of some arachidonic acid vasoconstric tor 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.