<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>A positive correlation has been established
between increased oxidative stress and cardiovascular
diseases in diabetes mellitus. We evaluated
the effects of single or combined treatments
with vitamin A (retinol acetate, 30
mg/kg/day, for 12-weeks) and insulin (8-10
IU/rat/day for the final 6-week) on vasomotor
activity, oxidative stress and retinol metabolism
in 12-week streptozotocin diabetic rats. The
vasomotor activity was determined by measuring
in <italic>vitro</italic> responsiveness of aorta rings to
phenylephrine (PE) and acetylcholine (ACh) in
the absence or in the presence of hydrogen peroxide
(H<sub>2</sub>O<sub>2</sub>). Preincubation with H<sub>2</sub>O<sub>2</sub> (10
μM) produced a significant decrease in PE (1
mM)-induced contraction in untreated-diabetic
but not in control rats. Single treatment with
insulin counteracted this effect of H<sub>2</sub>O<sub>2</sub> and
also reversed the increased contractile response
of diabetic aorta to PE, while vitamin A was
found to be ineffective. H<sub>2</sub>O<sub>2</sub> (10 μM) also
inhibited ACh (1 mM)-stimulated endothelium-
dependent relaxation two fold more in diabetic
than in control aorta. In the prevention of
H<sub>2</sub>O<sub>2</sub>-induced inhibition of vascular relaxation
to ACh, vitamin A alone was markedly effective
while insulin alone was not. The combination
of vitamin A plus insulin removed the
inhibitory action of H<sub>2</sub>O<sub>2</sub> in diabetic aorta.
Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance
(TBARS) in association with decreased levels of
plasma retinol and retinol-binding protein
(RBP). Single treatment with insulin, in spite of
allowing recovery of normal growth rate and
improved glucose and retinol metabolism in
diabetic rats, was unable to control TBARS
production to the same extent as vitamin A
alone. Our findings suggest that the maintenance
of ACh-stimulated endothelium-dependent
vasorelaxant tone in normal physiological
levels depends largely on the prevention and/or
inhibition of peroxidative stress, which is
achieved by combined treatment with vitamin
A plus insulin. The use of vitamin A together
with insulin provides a better metabolic control
and more benefits than use of insulin alone in
the reduction of diabetes-induced vascular
complications.</p>
[]
Int J Exp Diabetes Res. 2002; 3(2):119-130