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PC09 Involvement of ET-1 in diabetic cardiomyopathy, vascular abnormality and nepropathy which are regressed by a novel endothelin receptor antagonist Dajisentan. De-zai DAI, Min JI 1 Research Division of Pharmacology, China Pharmaceutical University, Nanjin 210009; 1Department of Pharmaceutical Chemistry, South-east University, Nanjing 210009, China. KEY WORDS diabetes; heart; blood vessels; kidney; endothelin antagonists AIM: An impaired endothelium contributes to diabetic cardiomyopathy CMP ; , vascular pathy VSP ; and nephropathy NPP ; in diabetes. It is hypothesized that these disorders which are the consequence to damaged endothelium could be recovered by Dajisentan, a novel dual endothelin receptor antagonist, developed by us as investigated new drug. METHODS: Rat diabetes model was developed by ip streptozotocin and the assessment of cardiomyopathy, vascular and renal abnormality were conducted in the absence and presence of long term treatment with Dajisentan po. RESULTS: An enhanced ET-1, iNOS activity and a reduction in NO were involved in the formation of the CMP, VSP, and NPP in diabetic rats. After 28 d treatment of po Dajisentan and aminoguanidine, an antagonist to AGEs and iNOS, the recovery of the CMP, VSP and NPP was significant and mediated by a reduction of ET-1 levels, iNOS activity and oxidative stress, and an increase in NO. The attenuation of urinary albumin and histological lesion in the kidney were remarkable in the treated group against the diabetic model. CONCLUSION: The onset of the CMP, VSP, and NPP is attributed to the compromized endothelium in diabetic rats. An endothelin antagonist Dajisentan which is very effective to relieve the pathogenesis from hyperglycemia offers a new approach to treat diabetes via a dual blockade on the ETA and ETB receptors. Project supported by the National Natural Science Foundation of China, No 30230170 and 30171078 and dilantin. Betnesol-n betamethasone, neomycin ; 5x 5ml drops customers who bought this product also bought the following products: zovirax acyclovir ; 200mg 30 pills depakot divalproex ; 250mg 30 pills nexium esomeprazole ; 20mg diflucan fluconazole ; 50mg 12 pills monopril fosinopril ; 20mg naprosyn naproxen ; 250mg xenical orlistat ; 120mg 30 pills inderal propranolol ; 80mg famvir famciclovir ; 250mg 30 pills zavedos idarubicin ; 10mg 1 pill product rating customer reviews there have been no reviews for this product. Head-to-head trials may need to be done by other entities, such as the national institutes of health and diovan.

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