Acute endothelium-mediated vasodilation is not impaired at the onset of diabetes.
Vascular 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 microg/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.
Brands
M W
MW
From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA. mbrands@physiology.umsmed.edu
Fitzgerald
S M
SM
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013311:Streptozocin; D000109:Acetylcholine