S. Vallejo et al., Treatment with acarbose may improve endothelial dysfunction in streplozotocin-induced diabetic rats, J CARDIO PH, 36(2), 2000, pp. 255-262
Citations number
31
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
We sought to determine whether a single reduction of hyperglycemia and thos
e derivatives from nonenzymatic protein glycosylation may be effective in r
educing the development of diabetic endothelial dysfunction. Therefore, we
investigated how acarbose, an inhibitor of intestinal alpha-glucosidase tha
t reduce hyperglycemia by lowering glucose absorption, may prevent the impa
irment of acetylcholine (ACh)-induced endothelium-dependent relaxations obs
erved in isolated vascular segments from untreated streptozotocin-induced d
iabetic rats. When administered after diabetes induction, 10 mg/kg acarbose
decreased modestly the enhancement of blood glucose and glycosylated hemog
lobin (HbA(1c)) levels, but not those of advanced glycosylation end product
s (AGEs). This effect was linked to a partial improvement of ACh-induced re
sponses both in conductance vessels. such as aortic segments, and resistanc
e vasculature, like mesenteric microvessels. When acarbose was introduced a
fter 6 weeks of untreated diabetes, blood glucose, HbA(1c), and AGE levels
were not affected and endothelial dysfunction remained unchanged in mesente
ric microvessels, whereas a small improvement was observed in aortic segmen
ts. The addition of 100 U/ml superoxide dismutase enhanced the impaired rel
axations to values similar to vessels from nondiabetic rats, indicating a m
ain role for superoxide anions in diabetes-induced endothelial dysfunction.
We conclude that hyperglycemia itself or elevated HbA(1c), but not plasma
AGEs, are related to enhanced oxidative stress and to the impairment of end
othelium function associated to diabetes. This process can be partially pre
vented by reducing glucose absorption with acarbose.