Abnormal protein expression in the corpus cavernosum impairs erectile function in type 2 diabetes.

OBJECTIVE: To investigate the changes in corporal relaxation, intracavernous pressure (ICP) and associated protein expression that control normal erectile function in rats with type 2 diabetes (T2D), as this disease is part of the 'metabolic syndrome' associated with a high rate of erectile dysfunction (ED) in men, resulting from failure of corpus cavernosum-mediated processes.
MATERIALS AND METHODS: T2D was induced in rats by feeding them with a high-fat diet (HFD) followed by an injection with low-dose streptozotocin (STZ); they were then compared with rats that received a normal diet (ND).
RESULTS: Hyperglycaemia and dyslipidaemia were induced in HFD + STZ rats, suggesting that T2D was established. The rats with T2D had associated ED, as both nonadrenergic noncholinergic-mediated corporal relaxation and increased ICP by cavernous nerve stimulation were significantly attenuated compared to the ND group. Western blot analysis revealed diabetes-associated lower expression of endothelial and neuronal nitric oxide synthase (e and nNOS), and cGMP-dependent protein kinase (PKG)-1alpha/beta expression in penile tissue than in the ND group. Contrary to the proteins that regulate corporal relaxation, there were relatively high levels of RhoA/Rho kinase receptor 1 (ROCK1) and ET-A receptor (ETAR) in T2D rats. However, the expressed level of phosphodiesterase-5 and insulin-like growth factor binding protein 3 was not altered significantly in response to T2D.
CONCLUSION: Decreased expression of certain proteins that mediate the relaxant mechanism, associated with increased expression of certain proteins that mediate contractile mechanisms, might be important in the development of T2D-associated ED. In particular, down-regulated eNOS/nNOS/PKG1 as well as up-regulated ETAR/RhoA/ROCK1 might participate in the aetiology of ED in T2D.