Selective nitrergic neurodegeneration in diabetes mellitus -: a nitric oxide-dependent phenomenon

1 In vitro and in vivo studies have demonstrated a dysfunctional nitrergic system in diabetes mellitus. thus explaining the origin of diabetic impotence. However, the mechanism of this nitrergic defect is not understood. 2 In the penises of streptozotocin (STZ)-induced diabetic rats, here, we show by immunohistochemistry that nitrergic nerves undergo selective degeneration since the noradrenergic nerves which have an anti-erectile function in the penis remained intact. 3 Nitrergic relaxation responses in vitro and erectile responses to cavernous nerve stimulation in vivo were attenuated in these animals, whereas noradrenergic responses were enhanced. 4 Activity and protein amount of neuronal nitric oxide synthase (nNOS) were also reduced in the penile tissue of diabetic rats. 5 We, thus, hypothesized that NO in the nitrergic nerves may be involved in the nitrergic nerve damage, since only the nerves which contain neuronal NO synthase underwent degeneration. 6 We administered an inhibitor of NO synthase, N-G-nitro-L-arginine methyl cater (L-NAME), in the drinking water of rats for up to 12 weeks following the establishment of diabetes with STZ. 7 Here we demonstrate that this compound protected the nitrergic nerves from morphological and functional impairment. Our results show that selective nitrergic degeneration in diabetes is NO-dependent and suggest that inhibition of NO synthase is neuroprotective in this condition.