Experimental chronic renal failure-associated erectile dysfunction: Molecular alterations in nitric oxide synthase pathway and IGF-I system

Chronic renal failure causes wide-ranging disturbances in male erectile fun ction, and the dysfunction usually is not corrected by hemodialysis, In thi s study, erectile function and expression of nitric oxide synthase (NOS) is oforms, insulin-like growth factor-I (IGF-I), and IGF-I binding proteins we re assessed in rats in which uremia had been produced by 5/6 nephrectomy, I n the animals that suffered renal failure, there was a significantly lower rise in intracavernosal pressure in response to electrical stimulation, and the mean patency period after cavernous nerve stimulation was significantl y increased. The amount of neuronial NOS mRNA was significantly higher in t he penile tissues and major pelvic ganglia (MPG) of uremic rats than in con trol animals. There consistently were higher levels of nNOS and endothelial NOS in the penile tissues and MPG of rats with renal failure, and there wa s a significant decrease in the amount of IGF-I gene expression in the MPG of these animals. Expression of the IGF binding proteins 2 and 4 but not 5 also was reduced. This preliminary work demonstrates that impairment of ere ction in chronic renal failure in the rat is attributable to a disturbance in NOS gene expression with concomitant changes in IGF-I, These discoveries may permit an improved therapeutic approach to men with erectile dysfuncti on associated with chronic renal failure.