Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide

作者：Zheng Hong; Liu Xuefei; Patel Kaushik P^*

来源：The Journal of Sexual Medicine, 2013, 10(9): 2165-2176.

DOI：10.1111/jsm.12248

• Type 1 Diabetes
• Central Nervous System
• Central Mechanisms of Penile Erection
• Erectile Dysfunction

Introduction Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. %26lt;br%26gt;Aim This study aims to determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)- and nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. %26lt;br%26gt;Methods Three weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol, or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks. %26lt;br%26gt;Main Outcome Measure Central NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats. %26lt;br%26gt;Results Two weeks of enalapril, losartan, or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responsesT1D+enalapril: 1.7 +/- 0.6, T1D+losartan: 2.0 +/- 0.3, T1D+tempol: 2.0 +/- 0.6 vs. T1D+vehicle: 0.6 +/- 0.3 penile erections/rat in the first 20 minutes, P%26lt;0.05; SNP responsesT1D+enalapril: 0.9 +/- 0.3, T1D+losartan: 1.3 +/- 0.3, T1D+tempol: 1.4 +/- 0.4 vs. T1D+vehicle: 0.4 +/- 0.2 penile erections/rat in the first 20 minutes, P%26lt;0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections, were also significantly increased in T1D rats after enalapril, losartan, or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased, and superoxide production was reduced in T1D rats after these treatments. %26lt;br%26gt;Conclusions These data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes to the dysfunction of central NMDA-induced erectile responses in T1D rats via stimulation of superoxide. Zheng H, Liu X, and Patel KP. Centrally mediated erectile dysfunction in rats with type 1 diabetes: Role of angiotensin II and superoxide. J Sex Med 2013;10:2165-2176.

• 出版日期2013-9