The role of endothelium-derived relaxing factors in mesenteric endothelial function in streptozocin-induced diabetic rats

We investigated the relative contribution of endothelium-derived relaxing factors (EDRFs) in mesenteric endothelial function in streptozocin (60 mg/kg, iv)-induced diabetic female rats. Endothelium dependent vasodilation (EDV) to acetylcholine (10?8 to 10?5 M) in rat mesenteric rings precontracted with phenylephrine (2 ?M) were obtained before and after pretreatment with indomethacin (indo, 10 ?M), a cyclooxygenase (COX) inhibitor, L-NAME (200 ?M), a nitric oxide synthase inhibitor, or barium chloride (100 ?M), a Kir channel blocker, with ouabain (10 ?M), a Na+-K+-ATPase inhibitor. Rings from diabetic rats relaxed less than those from controls. In controls, indo slightly decreased EDV. However, in diabetic group, indo tended to enhance it. Addition of L-NAME significantly reduced indo-resistant vasodilation in diabetes, but the added effect of L-NAME was not shown in controls. The remaining indo and L-NAME-resistant vasodilation was fully abolished by the combination of barium and ouabain in both groups. In conclusion, mesenteric EDV is impaired in diabetic female rats compare to that in controls. The effect of COX metabolites seems to be opposite in diabetic and control groups. Nitric oxide (NO) plays more role in mesenteric EDV in diabetic rats. However, when other pathways are blocked, endothelium-derived hyperpolarizing factor (EDHF) makes a greater contribution in controls (Supported by NIDCR)