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Calcium dobesilate increases endothelium-dependent relaxation in endothelium-injured rabbit aorta
1Department of Pharmacology, School of Medicine, Complutense University, Madrid, 28040, Spain.
Insights
Calcium dobesilate (DOBE) improves vascular health by restoring endothelial function in injured rabbit aortas. This angioprotective agent demonstrated significant restoration of endothelium-dependent relaxation after 30 days of treatment in an ex vivo model.
Area of Science:
- Pharmacology
- Vascular Biology
- Biochemistry
Background:
- Calcium dobesilate (DOBE) is an orally administered angioprotective agent used for vascular diseases like diabetic retinopathy.
- Its precise mechanism of action, particularly in restoring endothelial function, requires further elucidation.
- Previous in vitro findings prompted an ex vivo investigation into DOBE's efficacy.
Purpose of the Study:
- To correlate in vitro findings with an ex vivo model of endothelium injury induced by vitamin D2 overdose.
- To investigate the effect of different Calcium dobesilate (DOBE) dosages on endothelial function in a rabbit model.
- To determine the time-dependent efficacy of DOBE in restoring vascular health.
Main Methods:
- Male New Zealand White rabbits were subjected to two treatment protocols: 10 days and 30 days.
- Endothelial injury was induced using vitamin D2 (200,000 IU/day) for the initial 2 days.
- Rabbits received varying doses of Calcium dobesilate (DOBE) (50 mg/kg/day or 500 mg/kg/day) post-injury.
- Vascular reactivity was assessed using cumulative concentration-response curves for norepinephrine (NA), acetylcholine (ACh), and sodium nitroprusside (SNP).
Main Results:
- Calcium dobesilate (DOBE) treatment shifted the norepinephrine (NA) concentration-response curve downwards in both protocols.
- Endothelium-dependent relaxation induced by acetylcholine (ACh) decreased in hypervitaminotic rabbits but was restored to normal levels in both DOBE-treated groups after 30 days (Protocol 2).
- Endothelium-independent relaxation induced by sodium nitroprusside (SNP) was only reduced in hypervitaminotic rabbits during the 10-day protocol (Protocol 1).
Conclusions:
- Calcium dobesilate (DOBE) demonstrates efficacy in restoring endothelial functionality in endothelium-injured rabbit aortas.
- A treatment duration of 30 days is necessary for DOBE to significantly restore endothelium-dependent relaxation.
- These findings support the angioprotective role of DOBE and highlight the importance of treatment duration for its therapeutic effect.
Abstract:
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.