EFFECTS OF CALCIUM DOBESILATE ON THE SYNTHESIS OF ENDOTHELIUM-DEPENDENT RELAXING FACTORS IN RABBIT ISOLATED AORTA

1 Some cardiovascular disturbances which occur in diabetics are a cons equence of alterations in vascular contractility as well as in endothe lium-dependent relaxation. 2 Calcium dobesilate (DOBE) is a drug used in diabetic retinopathy and its mechanism of action is not yet underst ood. 3 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 iso lated aorta. 4 Endothelium-dependent relaxation induced by acetylcholi ne (ACh) (10(-8)-10(-5) M) increased in the presence of DOBE 10(-5) M only when vascular endothelium was kept intact. 5 N-G-nitro-L-arginine methyl ester (L-NAME; 10(-8)-10(-4) M progressively decreased the enh ancing effect of DOBE on endothelium-dependent relaxation whereas it w as progressively increased by L-Arg. 6 DOBE 10(-5) M increased in a no n-significant manner endothelium-dependent relaxation induced by ACh w hen the arteries were incubated with both L-NAME 10(-4) M and indometh acin 10(-6) M. 7 DOBE (10(-6) M and 10(-5) M) was able to scavenge sup eroxide anion radicals generated by the hypoxanthine/xanthine oxidase reaction. 8 These results provide evidence that DOBE is able to affect the vascular disorders associated with diabetes mellitus since it enh ances the synthesis of endothelium-dependent relaxing factors.