From the Department of Physiology and Biophysics, University of
Mississippi Medical Center, Jackson, Miss.
Correspondence to Michael W. Brands, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216. E-mail mbrands{at}physiology.umsmed.edu
AbstractVascular injury and
impaired vascular function are central to the increased mortality
associated with diabetes. Hyperglycemia in diabetes has been suggested
to play a role in this process, in part by impairing the function of
the vascular endothelium. It has been difficult,
however, to isolate the direct effect of glucose in both humans and in
animal models of diabetes. This was evaluated in the present study
in 7 rats that were chronically instrumented with a Transonic flow
probe at the iliac bifurcation of the abdominal aorta, a nonoccluding
catheter inserted immediately anterior to the flow probe, and a femoral
vein catheter. Acute infusions of acetylcholine and sodium
nitroprusside (1 and 10 µg/min IA) increased hindquarter blood flow
significantly by approximately 27 and 10 mL/min over baseline,
respectively, at the high dose. Streptozotocin (70 mg/kg IV) was
administered, but normoglycemia was maintained with continuous
intravenous insulin infusion to control for potential
streptozotocin side effects. Diabetes was induced 5 to 7 days later by
stopping the insulin infusion. Hindlimb blood flow (measured 24 hours
per day) decreased during the diabetic period and was accompanied by an
increase in mean arterial pressure, suggesting a
vasoconstrictor response. However, the responses to acetylcholine and
sodium nitroprusside were not altered significantly on either day 2 or
day 6 of the diabetic period. This suggests that neither
endothelium-mediated vasorelaxation nor responsiveness
to nitric oxide is impaired during the initial phase of diabetes and
that diabetic hyperglycemia does not have a significant, direct effect
to impair endothelium-mediated relaxation in
insulin-dependent diabetes mellitus. The mechanism for the change in
baseline blood flow and its potential influence on
endothelial function, however, are not known.
© 1998 American Heart Association, Inc.
Scientific Contributions
Acute Endothelium-Mediated Vasodilation Is Not Impaired at the Onset of Diabetes
Key Words: endothelium-derived relaxing factor blood flow diabetes glucose vasodilation nitric oxide
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