Study of calcium dobesilate in diabetic rats

Abstract

According to the World Health Organization (WHO) 74% of diabetic patients die of vascular complications. Previous reports have shown that endothelium-dependent relaxation of diabetic vasculature is more sensitive to free radical-induced injury. Calcium dobesilate (DOBE) has been successfully used in the treatment of diabetic retinopathy. The aims of this study were to investigate thein vivo andex vitro effects of DOBE on both contractile and relaxing responses in isolated diabetic rat aorta. Four groups of rats were used: Wistar rats (Group 0); spontaneously diabetic rats (BB/wor rats) (Group 1); BB/wor rats treated with DOBE 50 mg/kg/day (Group 2); and BB/wor rats treated with 500 mg/kg/day (Group 3). At 180 days after the development of diabetes, the animals were killed and the thoracic aorta were isolated, cleaned off, and mounted in an organ chamber. Two groups of experiments were carried out. In the first group (in vitro), incubation with DOBE 10⁻⁴ in aortic rings isolated from BB/wor rats decreased the contraction induced by noradrenaline (NA) 10⁻⁶ M (1.21±0.11 g vs 0.67±0.01 gP<0.01, n=8 in diabetic rings with or without the presence of DOBE 10⁻⁴ M, respectively), and this decrease was prevented by propranolol 10⁻⁶ M (1.20±0.6 g). DOBE 10⁻⁵ and 10⁻⁴ M increased the endothelium-dependent relaxation induced by ACh in BB/wor rats [the maximal relaxation with ACh 10⁻⁵ M was 50.0±5.1 vs 72.0±11.0 (p<0.05, n=8) and 69.0±7.8 (p<0.05, n=8) in BB/wor rats and after the incubation with DOBE 10⁻⁵ and 10⁻⁴ M, respectively], however, incubation with DOBE did not modify the endothelium-independent relaxation in these rats. In the second part of the study (ex vitro), we found an increase in the endothelium-dependent relaxation in arteries from diabetic rats treated with DOBE (Groups 2) compared with Group 1 (BB/wor rats) although we did not find any improvement in the endothelium-independent relaxation. Thus, in spontaneously diabetic rats, DOBE restored endothelium-dependent, but not independent, relaxation to normal and also decreased the contractile responses induced by NA through a mechanism that involves β-adrenergic receptors.