Advanced glycation end-products are responsible for the impairment of corpus cavernosal smooth muscle relaxation seen in diabetes

Objective To determine if advanced glycation products (AGEs) are responsibl e for the lower neuronal and endothelial-derived nitric oxide (NO)mediated relaxation of corpus cavernosum in tissue in diabetic rats than in control rats. Materials and methods Diabetes was induced in male Wistar rats by an intrap eritoneal injection with streptozotocin (60 mg/kg). One group of diabetic r ats was given free access to water and standard diet. A second group was gi ven standard diet and aminoguanidine with their water (50 mg/100 mL) from t he initiation of diabetes. Two groups of rats that were not diabetic acted as age-matched controls. After 8 weeks animals were killed by cervical disl ocation, corpus cavernosal tissue strips harvested and in an organ bath to measure isometric After 90 min of equilibration at optimal resting tension and contraction with 1 mu mol/L noradrenaline, the response to either acety lcholine or electrical field stimulation (EFS) after adding guanethidine (5 mu mol/L) and atropine (1 mu mol/L) was determined for each group. Results There was no difference between the baseline characteristics of all the experimental groups. After 8 weeks the mean body mass and glycosylated haemoglobin (HbA(1c)) were significantly greater in the diabetic than in c ontrol animals. Aminoguanidine had no effect on the recorded body mass or H bA(1c). The in vitro relaxation response to the application of acetylcholin e or EFS of tissue strips from age-matched control animals fed a standard d iet and those supplemented with aminoguanidine were the same. The administr ation of aminoguanidine to diabetic animals for 8 weeks reversed the expect ed impaired relaxation response to acetylcholine; the response to EFS was s imilar. Conclusion AGEs are more prevalent in erectile tissue from diabetic than in control animals. Aminoguanidine reversed the impairment in neuronal and en dothelial NO-mediated penile smooth muscle relaxation seen in diabetes. As aminoguanidine prevents AGE formation, erectile dysfunction in diabetes is probably caused partly by the generation of AGEs.