CALCIUM DOBESILATE INCREASES ENDOTHELIUM-DEPENDENT RELAXATION IN ENDOTHELIUM-INJURED RABBIT AORTA

Calcium dobesilate (DOBE) is an orally administered angioprotective ag ent which is used in some vascular diseases such as diabetic retinopat hy, although its mechanism of action is not yet fully understood. The aim of this work was to correlate previous 'in vitro' findings carried out in our laboratory with an 'ex vivo' model of endothelium-injury b y overdose of vitamin D-2. Male New Zealand White rabbits were used. T he study was divided into two protocols. Protocol 1: 10 days of treatm ent; and Protocol 2: 30 days of treatment. Rabbits in each group were treated with vitamin D-2 (200000 IU day(-1)) for the first 2 days and two groups were subsequently treated with DOBE at different doses (50 mg kg(-1) per day or 500 mg kg(-1) per day). The concentration-respons e curve induced by NA (10(-8)-10(-4) M) in aorta arteries was shifted downwards in the groups treated with DOBE (in both Protocol 1 and 2), whereas only in Protocol 2 (30 days of treatment) was this curve affec ted in the hypervitaminic group. The endothelium-dependent relaxation induced by ACh (10(-8)-10(-5) M) decreased in the hypervitaminic group s (in both Protocol 1 and 2) but only in Protocol 2 (30 days of treatm ent) was the endothelium-dependent relaxation restored to normal (cont rol, untreated group) in both DOBE-treated groups. The endothelium-ind ependent relaxation induced by sodium nitroprusside (SNP) (10(-8)-10(- 4) M) decreased in the hypervitaminic groups only in Protocol 1. We di d not find differences in the DOBE-treated groups in any protocol comp ared with the control (untreated) group. These findings show evidence that DOBE restored endothelial functionality in endothelium-injured ra bbit aorta only after 30 days of treatment. (C) 1998 The Italian Pharm acological Society.