Lack of central nitric oxide triggers erectile dysfunction in diabetes.
Erectile dysfunction is a serious and common complication of diabetes mellitus. The proposed mechanisms for erectile dysfunction in diabetes include central and autonomic neuropathy, endothelial dysfunction, and smooth muscle dysfunction. The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in centrally mediated penile erection. This study was designed to examine the role of nitric oxide (NO) within the central nervous system component of the behavioral responses including erection in diabetic rats. N-methyl-D-aspartic acid (NMDA)-induced erection, yawning, and stretch through the PVN can be blocked by prior administration of NO synthase (NOS) blocker, L-NMMA, in freely moving, conscious male normal rats. Four weeks after streptozotocin (STZ) and vehicle injections, NMDA-induced erection, yawning, and stretch responses through the PVN are significantly blunted in diabetic rats compared with control rats. Examination of neuronal NOS (nNOS) protein by Western blot analysis indicated a reduced amount of nNOS protein in the PVN of rats with diabetes compared with control rats. Furthermore, restoring nNOS within the PVN by gene transfer using adenoviral transfection significantly restored the erectile and yawning responses to NMDA in diabetic rats. These data demonstrate that a blunted NO mechanism within the PVN may contribute to NMDA-induced erectile dysfunction observed in diabetes mellitus.
Zheng
Hong
H
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.
Bidasee
Keshore R
KR
Mayhan
William G
WG
Patel
Kaushik P
KP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015000:Yawning / Q000187:drug effects / Q000502:physiology
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D016202:N-Methylaspartate; D052248:Nitric Oxide Synthase Type I