Vasodilator prostanoids compensate for attenuated nitric oxide mediated vasodilation in type 1 diabetes

Abstract

Background Previous research examining endothelial function and the biochemical pathways mediating vasodilation in type 1 diabetes has been conflicting. Both impaired and preserved nitric oxide (NO) mediated vasodilation have been reported whilst some authors have suggested enhanced vasodilator prostanoid (P) activity. The aim of this study was to determine the relative contributions of NO and P to endothelial function in a homogenous group of type 1 diabetic patients free of other confounding factors that may influence vascular behaviour.^f ^ Methods and results Endothelial function was assessed using forearm venous plethysmography in 16 patients with uncomplicated type 1 (duration of diabetes 16.8±2.5 years (mean±SEM), HbA1C 7.53±0.21% ) and 15 non-diabetic age and sex matched healthy control subjects. Forearm responses to the endothelium-dependent vasodilator, acetylcholine (ACh) (7.5, 15 and 30 µg/min), were recorded at baseline and after intra-arterial infusion of L-NMMA (a NO synthase inhibitor). Responses to ACh were re-examined following co-infusion of L-NMMA and indomethacin (a cyclo-oxygenase inhibitor). Responses to ACh were calculated as areas under the curve (AUC). At baseline vasodilator responses to ACh were similar (p=0.3) in diabetic and non-diabetic subjects. However, L-NMMA reduced ACh mediated responses to a lesser extent in diabetic subjects than control subjects (3±6% versus 18±3%; p<0.03 respectively). Co-infusion with indomethacin further reduced blood flow, but the relative decrease in AUC was greater in the diabetic group (28±3% vs. 14±3%; p<0.001). The contribution of biochemical pathways other than NO and P were similar in both diabetic and control groups (69±7% vs. 68±4%; p=0.45). Conclusions Vasodilator responses to ACh were unchanged in type 1 diabetes but this was reliant up on enhanced P mediated activity compensating for attenuated NO activity. Furthermore, vasoactive substances in addition to NO and P contribute significantly to vascular tone in both diabetic and non-diabetic subjects.