Calcium dobesilate increases endothelium-dependent relaxation in endothelium-injured rabbit aorta.
Calcium dobesilate (DOBE) is an orally administered angioprotective agent which is used in some vascular diseases such as diabetic retinopathy, although its mechanism of action is not yet fully understood. The aim of this work was to correlate previous rising single quote, left (low)in vitro' findings carried out in our laboratory with an rising single quote, left (low)ex vivo' model of endothelium-injury by overdose of vitamin D2. Male New Zealand White rabbits were used. The study was divided into two protocols. Protocol 1: 10 days of treatment; and Protocol 2: 30 days of treatment. Rabbits in each group were treated with vitamin D2 (200"000 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-response 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 affected in the hypervitaminic group. The endothelium-dependent relaxation induced by ACh (10(-8)-10(-5) M) decreased in the hypervitaminic groups (in both Protocol 1 and 2) but only in Protocol 2 (30 days of treatment) was the endothelium-dependent relaxation restored to normal (control, untreated group) in both DOBE-treated groups. The endothelium-independent relaxation induced by sodium nitroprusside (SNP) (10(-8)-10(-4) M) decreased in the hypervitaminic groups only in Protocol 1. We did not find differences in the DOBE-treated groups in any protocol compared with the control (untreated) group. These findings show evidence that DOBE restored endothelial functionality in endothelium-injured rabbit aorta only after 30 days of treatment. (c) 1998 The Italian Pharmacological Society.
Ruiz
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Department of Pharmacology, School of Medicine, Complutense University, Madrid, 28040, Spain.
Tejerina
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002123:Calcium Dobesilate / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004872:Ergocalciferols; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014652:Vascular Diseases / Q000139:chemically induced / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D004872:Ergocalciferols; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D002123:Calcium Dobesilate; D000109:Acetylcholine