Small Artery Function in Streptozotocin-Induced Diabetic Rats

There is growing evidence to suggest that dysfunction of the endothelium may contribute to many of the vascular complications of diabetes. The high incidence of hypertension, accelerated atherosclerotic processes and increased coagulability of the blood in diabetes all indirectly suggest involvement of the endothelium. The earliest direct evidence came from the isolated corpora cavernosa obtained from diabetic men (1), which showed abnormal relaxation to acetylcholine and suggested that reduced endothelial production of nitric oxide (NO) may play a role in impotence. More recent studies using forearm plethysmography have shown reduced endothelium-dependent relaxation in diabetic subjects (2,3) and, in the vasculature of animals with chemically induced diabetes, relaxation to acetylcholine has frequently been reported as abnormal (4). Further investigations, predominantly in the diabetic rabbit model (5), have suggested that the defect does not lie in reduced NO synthesis, but is associated with constrictor prostaglandin production, and a related rise in free radical generation. In turn, this has been attributed to the effects of hyperglycaemia (6). Most of the studies in animal models in diabetes have however used conduit arteries, which may have limited relevance to the vascular complications of diabetes (other than atherosclerosis). In our laboratory we have recently carried out a number of investigations (7,8,9) using resistance sized arteries obtained from rats in which diabetes had been induced by injection of streptozotocin (STZ). We have studied endothelial function, responses to constrictor agonists and the role of a number of biochemical pathways which have been implicated in endothelial dysfunction. In addition we have investigated the effect of hyperglycaemia on endothelial function in normal arteries. These investigations are summarized below. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.