Nitric oxide and penile erection in streptozotocin-diabetic rats

The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ )-diabetic Sprague-Dawley rats, and the function of the NO-generating syste m in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague-Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by m easuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was d etermined in corporal tissue by measuring the generation of [H-3]citrulline from [H-3]arginine. Copulation-induced erection was inhibited at and 2 mon ths after STZ treatment, but th is could be prevented by a short (2-week) p retreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 mo nths after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a a-week, but not by a I-week, pretreatment with insulin; however, at 9 month s after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots i n pithed rats was enhanced in diabetic animals. Th is enhancement was also normalized at 4 months, bur not at 9 months, by 2 weeks of insulin treatmen t. The inhibition of the stimulation-induced increase in corporal pressure by N-G-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6-8 months of diabetes, In conclusion, STZ-induced diabetes cause d changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irrevers ible. NO synthase activity in cavernosal tissue was normal, but the respons e to N-G-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).