Effects of calcium dobesilate on the synthesis of endothelium‐dependent relaxing factors in rabbit isolated aorta

Some cardiovascular disturbances which occur in diabetics are a consequence of alterations in vascular contractility as well as in endothelium‐dependent relaxation. Calcium dobesilate (DOBE) is a drug used in diabetic retinopathy and its mechanism of action is not yet understood. The aim of this study was to investigate the effects of DOBE on synthesis and release of endothelium‐dependent relaxing factor (EDRF) and endothelium‐dependent hyperpolarizing factor (EDHF) in rabbit isolated aorta. Endothelium‐dependent relaxation induced by acetylcholine (ACh) (10 −8 –10 −5 M ) increased in the presence of DOBE 10 −5 M only when vascular endothelium was kept intact. N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME; 10 −8 –10 −4 M progressively decreased the enhancing effect of DOBE on endothelium‐dependent relaxation whereas it was progressively increased by L ‐Arg. DOBE 10 −5 M increased in a non‐significant manner endothelium‐dependent relaxation induced by ACh when the arteries were incubated with both L ‐NAME 10 −4 M and indomethacin 10 −6 M . DOBE (10 −6 M and 10 −5 M ) was able to scavenge superoxide anion radicals generated by the hypoxanthine/xanthine oxidase reaction. These results provide evidence that DOBE is able to affect the vascular disorders associated with diabetes mellitus since it enhances the synthesis of endothelium‐dependent relaxing factors.British Journal of Pharmacology (1997) 121 , 711–716; doi: 10.1038/sj.bjp.0701184