Mechanisms underlying defective aorta and corpus cavernosum function in experimental diabetes
Diabetic patients have an increased risk of developing both micro- and macrovascular complications. It is thought that the primary lesion in the genesis of these complications is at the level of the vascular endothelium. The effects of diabetes on endothelial function can be monitored in vitro using aortae isolated from streptozotocin-diabetic rats. This project found that two months of untreated diabetes resulted in a profound deficit in maximum endothelium-dependent relaxation to cumulative doses of acetylcholine in phenylepherine precontracted aortae. Treatment of rats with the antioxidants vitamin E and trientine from the induction of diabetes prevented the development of the deficit in endothelium-dependent relaxation, suggesting that increased levels of oxidative stress in diabetes contribute to abnormal endothelial function. Compensation for impaired essential fatty acid metabolism in diabetic rats with evening primrose oil partially prevented the development of defective aortic endothelium-dependent relaxation, implication this hyperglycaemia-induced metabolic disturbance in diabetic endothelial dysfunction. Diabetes is also associated with impaired penis erectile performance and importance in animals and patients. An in vitro preparation was developed to examine the effects of streptozotocin-induced diabetes on chemical stimulation of the endothelium and electrical stimulation of the autonomic nerves of rat corpus cavernosum. Both endothelium and neurally mediated relaxation responses were found to be impaired in two month untreated diabetic rats. Treatment of diabetic rats with the antioxidants α-lipoic acid and trientine prevented the formation of defective endothelium and nerve relaxation responses, thus implicating oxidative stress in the pathogenesis of these impairments. Inhibition of defective polyol pathway activity also prevented the development of reduced endothelium and nitrergic nerve responses, thus suggesting a role for this role for this well studied metabolic abnormality in impaired corpus cavernosum function in experimental diabetes.