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-induced skeletal muscle blood flow in young subjects with Type I (insulin-dependent) diabetes mellitus compared with healthy controls. Both NO and prostanoids are important regulators of vascular tone and may therefore contribute to this hyperaemia. The aim of the present study was to determine the contribution of NO and vasodilator prostanoids to this skeletal muscle hyperaemia 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 N(G)-monomethyl-L-arginine (L-NMMA) on skeLetal muscle blood flow in subjects with Type I diabetes mellitus (DM subjects) and control subjects. Blood flow was measured by venous occlusion plethysmography. Isotonic forearm exercise involved 2 min of wrist flexion and extension. Resting flow (forearm blood flow; FBF) was augmented in DM subjects, 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-time 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 29% (P<0.05) and 39% (P<0.0005) respectively in controls, but had no significant 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 subjects (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 Type I diabetes.
Skyrme-Jones
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RA
Centre for Heart and Chest Research, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia.
O'Brien
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RC
Meredith
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IT
D000328:Adult; D019540:Area Under Curve; D001241:Aspirin / Q000494:pharmacology; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001241:Aspirin