Vasodilator prostanoids, but not nitric oxide, may account for skeletal muscle hyperaemia in type I diabetes mellitus

We and others have previously documented increased resting and exercise-ind uced skeletal muscle blood flow in young subjects with Type I (insulin-depe ndent) diabetes mellitus compared with healthy controls. Both NO and prosta noids are important regulators of vascular tone and may therefore contribut e to this hyperaemia. The aim of the present study was to determine the con tribution of NO and vasodilator prostanoids to this skeletal muscle hyperae mia in diabetes. We assessed the effects of infusion into the intrabrachial artery of the cyclo-oxygenase inhibitor acetylsalicylic acid (ASA; aspirin ) and of the L-arginine analogue NG-monomethyl-L-arginine (L-NMMA) on skele tal muscle blood flow in subjects with Type I diabetes mellitus (DM subject s) and control subjects. Blood flow was measured by venous occlusion plethy smography. Isotonic forearm exercise involved 2 min of wrist flexion and ex tension. Resting flow (forearm blood flow; FBF) was augmented in DM subject s, as was peak exercise-related blood flow (PFBF) and the volume repaid to the forearm 5 min after exercise (AUC 5, where AUC is area under the flow-t ime curve) (P < 0.05), even when accounting for differences in basal flow, infusion of L-NMMA reduced resting flow by 48% in controls (P < 0.005) and by 12% in DM subjects (not significant). L-NMMA reduced PFBF and AUC 5 by 2 9% (P < 0.05) and 39% (P < 0.0005) respectively in controls, but had no sig nificant effect on these parameters in DM subjects. Infusion of ASA reduced FBF, PFBF and AUC 5 in both DM (P < 0.05) and control (P < 0.05) subjects, but the magnitude of this reduction was greater in DM than in control subj ects (ANOVA, P < 0.05), even when differences in resting FBF were accounted for. Indeed, ASA eliminated the differences in FBF, PFBF and AUC 5 between DM and control subjects. Thus increased release of vasodilator prostanoids , rather than of NO, appears to account for skeletal muscle hyperaemia in T ype I diabetes.