beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes

The effect of beta antagonists in the diabetic vascular lesion is controversial. We investigated the effect of celiprolol hydrochloride, a beta1 antagonist and mild beta2 agonist, on the lesions and function in type II male Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats. OLETF rats were fed regular chow with or without atenolol (25 mg/kg/day) or celiprolol (100 mg/kg/day) treatment (group DM, no treatment; group DM-a, atenolol treatment; group DM-c, celiprolol treatment), and treatment was continued for 31 days. Separately, normoglycemic control rats, LETO, were prepared as group C. On day 3, endothelial cells of the right internal carotid artery were removed by balloon injury, and the rats were evaluated 4 weeks after balloon injury. The plasma glucose and lipid levels were unchanged throughout the treatment period. Intimal thickening was observed in the right carotid artery in the DM and DM-a groups; however, little thickening was observed in those of DM-c rats. Acetylcholine-induced NO-dependent relaxation in arteries was improved in DM-c rats compared with DM and DM-a rats (maximum relaxation DM 30.8+/-4.5, DM-a 37.4+/-3.9, DM-c 48.8+/-4.6%, *P