Arteriolar changes in nitric oxide activity and sensitivity during the course of streptozotocin-induced diabetes

Nitric oxide (NO) may play an important role in the pathogenesis of diabetic microangiopathy. However, arteriolar changes in NO activity and sensitivity to NO may be dependent on both the type of arteriole and the duration of diabetes. Therefore, we assessed, in the in situ spinotrapezius muscle preparation of streptozotocin-diabetic rats and of controls, inside diameters of A2-A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after N(G)-nitro-L-arginine (L-NNA) at 2, 4, 6 and 12 weeks of diabetes. In A2 arterioles, basal diameters and the contribution of NO to basal diameter were not affected during the course of streptozotocin-induced diabetes. However, the maximal response to acetylcholine in these arterioles was attenuated after 2 until 4 weeks, and from 4 weeks on a sustained decrease in reactivity to sodium nitroprusside was observed. In A3 arterioles, both the basal diameter and the contribution of NO to basal diameter were decreased after 2 weeks and increased after 6 weeks, while the response to sodium nitroprusside was unaffected. In A4 arterioles, a significant increase in basal diameter was observed after 6 weeks only. Thus, this study shows that streptozotocin-induced diabetes causes microvascular changes in NO activity and sensitivity that depend on the type of arteriole. For each order of arteriole, these changes show a specific pattern during the course of diabetes.