(Hypertension. 1999;34:1080-1085.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Elevated Skeletal Muscle Blood Flow in Noncomplicated Type 1 Diabetes Mellitus
Role of Nitric Oxide and Sympathetic Tone
From the Departments of General Internal Medicine (G.V., J.A.L., P.S.), Nephrology (J.F.W., J.H.B.), and Pharmacology (P.S.), University Hospital Nijmegen St Radboud, Nijmegen; and the Department of Internal Medicine (L.G.D.), TweeSteden Hospital, Tilburg, the Netherlands.
Correspondence to Gerald Vervoort, MD, University Hospital Nijmegen St Radboud, Division of General Internal Medicine 541, Geert Grooteplein 8, PO Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail g.vervoort{at}aig.azn.nl
Abstract—Capillary
hyperperfusion precedes and contributes to the occurrence of diabetic
microangiopathy. Vascular tone is regulated by the balance of
vasodilating and vasoconstricting factors, of which nitric oxide (NO;
an endothelium 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 patients with noncomplicated type 1 diabetes (DP) and 50 healthy
control subjects (CS) under baseline conditions and during
intrabrachial infusion of
NG-monomethyl-L-arginine
(L-NMMA), an endothelium-dependent vasoconstrictor, and
acetylcholine (ACh), an endothelium-dependent
vasodilator. Furthermore, we determined arterial plasma NE
concentration at baseline and then determined 
-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 flow 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 versus 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 noncomplicated type 1 diabetes. We found no evidence of a
disturbance of basal or stimulated NO production.
Arterial plasma NE concentrations are decreased in
noncomplicated type 1 diabetes. This may explain the vasodilatation at
baseline and the increased vascular response to
intra-arterially NE.
Key Words: endothelium • L-NMMA • norepinephrine • acetylcholine • diabetes • blood flow
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