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

Abstract

Introduction Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. Aim To determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)-nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. 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. 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. 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 responses – T1D+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 min, P < 0.05; SNP responses – T1D+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 min, P < 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. 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.

EFFECT OF TEMPOL ON REDOX HOMEOSTASIS AND STRESS TOLERANCE IN MIMETICALLY AGED DROSOPHILA

“…Nonetheless, the possible proposed biochemical mechanism overwhelming mitochondrial oxidative stress of tempol is attributed to hydroxylamine reduction of tempol as well as nitroxide formation (Wang et al., ; Wilcox, ). Moreover, tempol has been reported to improve chronic high salt intake induced kidney injury (Carlström et al., ), and to be effective in preventing several of the adverse consequences of oxidative stress (Wilcox, ), and type 1 diabetes induced organ injury (Zheng et al., ) in animal models. Here, we demonstrated beneficial effects on alleviation of oxidative protein damage by tempol and stress tolerance in mimetic aging model of Drosophila .…”

Effects of exercise on sexual function and central mechanism in the streptozotocin-induced diabetic rats

“…Exercise up-regulated nNOS expression within the PVN and improved the central component of the erectile dysfunction in diabetes mellitus ( Zheng et al, 2011 ). The level of neuronal NOS in the PVN was decreased in STZ-induced type 1 diabetic rats ( Zheng et al, 2013 ).…”

Modulation of Dopaminergic Pathways to Treat Erectile Dysfunction

“…NMDA stimulates the same oxytocinergic pathways as dopamine, and there was ED and reduced expression of neuronal NOS in PVN . The authors found that both exercise and treatment with angiotensin II type 1 (AT 1 ) receptor antagonists improve erectile function in the streptozocin‐induced diabetic rat model , but the effect of dopaminergic drugs on erectile function remains to be investigated in animal models with diabetes.…”