The role of the renin-angiotensin system in the aetiology of experimental diabetic neuropathy
Lisinipril can have a hypotensive effect in normotensive patients, therefore it is desirable to investigate a renin-angiotensin system (RAS) antagonist without this side effect. It is also necessary to examine the role of the RAS in the aetiology of experimental diabetic neuropathy, as it is hoped that through a better understanding of the disease process an effective treatment for this diabetes related complication will transpire. Nerve function and neurovascular status were examined in (STZ)-diabetic rats either with or without treatment with one of two angiotensin II receptor antagonists (ZD 8731, or ZD 7155). Both antagonists improved sciatic nerve function and promoted endoneurial angiogenesis in this model. ZD 7155 also prevented the neurovascular deficits associated with experimental diabetes. In addition, in acute experiments ZD 8731 increased whole sciatic nerve blood flow and reduced vascular resistance in STZ-diabetic rats. This indicates that experimental diabetes alters the RAS leading to diminished nerve function and vascular status. The vascular reactivity of the vasa nervorum to vasoconstrictor agonists such as angiotensin II was found to be elevated whereas, the reactivity to acetylcholine was diminished in STZ-diabetic rats. ACE activity was also found to be increased in these animals. Therefore, these factors are likely to play part in RAS changes. Further studies examining anti-oxidant and pro-oxidant treatment suggested that the mechanism by which the changes in the RAS develop is related to increases in oxidative stress. To conclude, the RAS is modified by experimental diabetes. These changes contribute to the neurovascular deficits found in dysfunctional diabetic nerve.