Elevated skeletal muscle blood flow in noncomplicated type 1 diabetes mellitus - Role of nitric oxide and sympathetic tone

Capillary hyperperfusion precedes and contributes to the occurrence of diab etic microangiopathy. Vascular tone is regulated by the balance of vasodila ting and vasoconstricting factors, of which nitric oxide (NO; an endotheliu m dependent vasodilator) and norepinephrine (NE; a potent vasoconstrictor), respectively, are of primary importance. To investigate the role of these factors in hyperperfusion, we measured forearm blood flow (FBF) in 50 patie nts with noncomplicated type 1 diabetes (DP) and 50 healthy control subject s (CS) under baseline conditions and during intrabrachial infusion of N-G-m onomethyl-L-arginine (L-NMMA), an endothelium-dependent vasoconstrictor, an d acetylcholine (ACh), an endothelium-dependent vasodilator. Furthermore, w e determined arterial plasma NE concentration at baseline and then determin ed alpha-adrenergic receptor sensitivity by measuring FBF response to intra -arterially infused NE. We found that basal FBF was increased in DP (2.9+/- 0.1 versus 2.0+/-0.1 mL . min(-1) . dL(-1) in CS; P<0.01). L-NMMA caused a similar vasoconstriction in both groups (28.5+/-1.7% in DP versus 31.2+/-2. 2% in CS; P=NS). Maximum blood now during infusion of ACh was not different (23.3+/-1.9 mL . min(-1) . dL(-1) in DP versus 20.1+/-1.6 in CS). Arterial plasma NE concentrations were significantly decreased in DP (0.57+/-0.03 v ersus 0.81+/-0.05 nmol/L in CS; P<0.01). The vasoconstrictive effect of NE was increased in DP (slope log dose-response curve, 31.3+/-1.5 versus 24.3/-1.8 in CS; P<0.01). We conclude that basal FBF is increased in noncomplic ated type 1 diabetes. We found no evidence of a disturbance of basal or sti mulated NO production. Arterial plasma NE concentrations are decreased in n oncomplicated type 1 diabetes. This may explain the vasodilatation at basel ine and the increased vascular response to intra-arterially NE.