The protective effect of aminoguanidine on erectile function in streptozotocin diabetic rats

Erectile dysfunction (ED) is frequently associated with diabetes mellitus. We determined if advanced glycation end products (AGEs) are involved in ED and investigated if the selective AGE and inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) could protect against the development of ED in a diabetic rat model.

Harlan Sprague-Dawley rats were divided into 3 groups. The 9 nondiabetic rats in group 1 served as age matched controls. Diabetes was induced in the 9 rats in groups 2 and 3, respectively, by intraperitoneal injection of streptozocin (60 mg/kg). While group 2 was given free access to water and a standard diet, group 3 was treated with AG added to drinking water (1 gm/l daily). Two months after diabetes induction in vivo intracavernous pressure measurements were determined. Penile tissue glycation (furosine on high performance liquid chromatography), AGEs (pentosidine on high performance liquid chromatography and immunohistochemistry), AGE receptor (galectin-3 on immunohistochemistry and Western blot) and iNOS (Western blot) levels were measured in control and diabetic penises.

Cavernous tissue furosine, pentosidine, galectin-3 and iNOS protein levels were significantly elevated in the diabetic group compared with controls (p <0.05). On the other hand, cavernous tissue furosine, pentosidine, galectin-3 and iNOS expression were lower in diabetic rats treated with AG despite an unchanged glycemia level. Diabetic rats had a significant decrease in erectile function compared with control rats (p <0.05), while AG treated diabetic rats showed erectile function similar to that in control animals.

Glycation, AGEs, galectin-3 and iNOS levels are elevated in diabetic rat penile tissue and significantly decreased by AG treatment. Furthermore, erectile function was preserved in AG treated animals. The observation that AG improved glycation despite no effect on glycemia suggests that AG may improve penile collagen turnover.