Although autonomic nerve testing is found to be abnormal in up to 63% of patients with diabetic ED, some studies have shown no difference from control values.
NO has been identified as the principal neurotransmitter causing the relaxation of penile cavernous smooth muscle. This smooth muscle relaxation increases arterial blood flow and produces an erection. It has been shown in diabetic rats that NO synthase, the enzyme that catalyses the production of NO in cavernosal tissue, decreased even with insulin treatment . The ED in these diabetic rats did not improve, suggesting that permanent nerve injury to the nonadrenergic, noncholinergic nerves may contribute to abnormal response.
Oxidative stress has recently been implicated in the pathogenesis of diabetic complications. The deleterious effects of high glucose concentrations on cultured Schwann or endothelial cells appear to be related, in part, to rates of glucose auto-oxidation to advanced glycosylation end products . In the course of glucose auto-oxidation, hydrogen peroxide is generated from molecular oxygen via the dismu-tation of superoxide anion, thus exerting an additional oxidative stress. The interaction of advanced glycosylation end products with sulfhydryl-containing proteins, altered prostanoid production, and ischemia/ reperfusion are further important sources of reactive oxygen species (ROS) in diabetic tissues. Interestingly, insulin itself may, under certain circumstances, activate a membrane-bound hydrogen peroxide generating system that could theoretically exacerbate oxidative stress in susceptible tissues. This oxidative stress, in turn, may conceivably exhaust local antioxidant defenses and thereby promote lipid peroxidation of cellular membranes, cytoskeletal damage and ultimately cellular degeneration. Furthermore, mitochondrial DNA mutations have been reported in diabetic tissues , suggesting oxidative stress-related mitochondrial damage. Attention has also been recently focused on the role of ROS in vascular dysfunction in diabetes — buy diabetes drugs, particularly regarding the reaction of NO with superoxide anion to form peroxynitrate, a very potent ROS .