REDUCTION OF PENILE NITRIC-OXIDE SYNTHASE IN DIABETIC BB WOR(DP) (TYPE-I) AND BBZ/WOR(DP) (TYPE-II) RATS WITH ERECTILE DYSFUNCTION/

Erectile dysfunction occurs frequently in human diabetes, and it is so metimes associated with hypogonadism. These conditions also develop in a model of insulin-dependent (type I) diabetes, the BB/WOR(dp) (diabe tic prone) rat but have not yet been investigated in the model of insu lin-resistant (type II) diabetes, the BBZ/WOR rat. It is also unknown whether diabetes-related impotence is due to reduced levels of the med iator of penile erection, nitric oxide, caused by a decrease of nitric oxide synthase (NOS) in the penis. To clarify these questions, groups (n = 5-6) of diabetic BB/WOR(dp) (insulin-maintained) and BBZ/WOR rat s were age-matched with diabetic-resistant BB/WOR(dr) and non-diabetic BB/WOR(dp) rats and submitted to determinations of serum glucose, tes tosterone, and penile reflexes (cups and flips). Erectile dysfunction was found in all of type I and in most of type II diabetic animals (gl ycemias of 25.0 and 31.1 mM), at the selected mean ages of 310 and 180 days old, respectively. This was evidenced by over 95% decreases of e rectile reflexes in both types of diabetes and was accompanied by 75% reduction of serum testosterone. Soluble NOS activity was measured in penile tissue from the diabetic rats with impaired erectile reflexes a nd in the corresponding controls, by the (3H)-L-arginine/citrulline co nversion assay. The neuronal NOS isoform (nNOS) content was determined by a semiquantitative western blot assay. Both types of diabetes show ed a marked decrease of penile NOS activity (74 and 55%, respectively) , and a lower reduction of penile nNOS content (47 and 33%, respective ly). No endogenous NOS inhibitor was detected in the diabetic type I p enile cytosol by cross-mixing NOS activity assays. Our data support a common etiology for erectile dysfunction present in rats with types I and II diabetes mellitus and suggest that the etiology is related to a decrease of penile NOS derived in part from serum androgen deficiency .