Ability of Cyclohexenonic Long-Chain Fatty Alcohol to Ameliorate Diabetes-Induced Cystopathy in the Rat

We investigated the pharmacological effects of N-hexacosanol on diabetic rat detrusor. Eight-week-old male Sprague-Dawley rats were randomly divided into 4 groups: diabetic rats induced by 50 mg/kg intraperitoneally of streptozotocin treated with N-hexacosanol (0, 2 or 8 mg/kg, subcutaneously every day) and control rats. Bladder function was estimated by functional studies using carbachol and KCl. Contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype-selective muscarinic antagonists, that is, atropine, pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). The participation levels of muscarinic M2 and M3 receptor mRNAs in detrusor were investigated by real-time polymerase chain reaction. Treatment with N-hexacosanol did not alter diabetic status of the rats, but significantly improved the diabetes-induced hypercontractility of the rat bladder. Estimations of the pA2 values for atropine, pirenzepine, methoctramine and 4-DAMP indicate that the carbachol-induced contractile response is mediated through the M3 receptor subtype in all groups. Furthermore, N-hexacosanol ameliorated the diabetes-induced upregulation of muscarinic M2 receptor mRNAs in streptozotocin-diabetic rat detrusor. Our data indicate that N-hexacosanol has therapeutic effects on hypercontractility in the diabetic bladder by ameliorating overexpression of muscarinic M2 and M3 receptor mRNAs without significant alternations of pharmacological profiles.