AB195. Role of PI3K/AKT in the erectile dysfunction from metabolic syndrome rats

OBJECTIVE: The metabolic syndrome, a disease arising from the world-wide epidemic of obesity, is manifested as insulin resistance, hypertension, hyperlipidaemia, and diabetes. Metabolic syndrome is a risk factor for erectile dysfunction (ED), but the underlying mechanisms are unclear. The aims of this study were to determine the underlying mechanisms of the metabolic syndrome-related ED. METHODS: Sprague-Dawley rats rendered obese by feeding a very high fat diet for 6 months. Body weight, plasma insulin and glucose levels (insulin-resistance) and plasma lipid were assessed. Erectile responses were evaluated by determining mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) with electrical stimulation of the cavernous nerve. Levels of protein expression were examined by Western Blot. Reactive oxygen species (ROS) production was measured by dihydroethidium (DHE) staining. RESULTS: The levels of body weight, blood glucose, plasma lipid were increased in metabolic syndrome rats when compared to those of control rats (P<0.05). The ratio of maximum ICP-to-MAP (max ICP/MAP) and the concentration of cyclic guanosine mono-phosphate (cGMP) was significantly decreased in metabolic syndrome ED rats, compared to that of age-matched control rats (P<0.05). Expression levels of p55, AKT and eNOS were reduced, compared to those of control rats (P<0.05). Expression levels of NADPH oxidase subunits p40phox was increased in metabolic syndrome rats when compared to those of control rats (P<0.05). ROS production was increased in metabolic syndrome rats when compared to that of control rats (P<0.05). CONCLUSIONS: Conclusions. The present study demonstrates PI3K/AKT induced oxidative stress and impaired endothelial NO signal pathway likely contribute to the metabolic syndrome-associated ED.