Centrally mediated erectile dysfunction in rats with type 1 diabetes: role of angiotensin II and superoxide

• Published in: Journal of sexual medicine Vol. 10; no. 9; p. 2165
• Main Authors: Zheng, Hong, Liu, Xuefei, Patel, Kaushik P
• Format: Journal Article
• Language: English
• Published: Netherlands 01.09.2013
• Subjects: Angiotensin II - metabolism; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Animals; Antioxidants - administration & dosage; Behavior, Animal; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - physiopathology; Erectile Dysfunction - etiology; Erectile Dysfunction - metabolism; Erectile Dysfunction - physiopathology; Excitatory Amino Acid Agonists - administration & dosage; Humans; Male; Nitric Oxide - metabolism; Nitric Oxide Donors - administration & dosage; Nitric Oxide Synthase Type I - metabolism; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular Hypothalamic Nucleus - physiopathology; Penile Erection - drug effects; Penis - drug effects; Penis - innervation; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction; Superoxides - metabolism; Erectile Dysfunction; Type 1 Diabetes; Central Mechanisms of Penile Erection; Central Nervous System
• ISSN: 1743-6109
• DOI: 10.1111/jsm.12248

Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. 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. 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. 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. 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 minutes, 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 minutes, 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. 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.