<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>Impaired vascular endothelium-dependent relaxation
and augmented contractile responses have been
reported in several models of long-term hyperglycemia.
However, the effects of short-term ambient
hyperglycemia are poorly understood. Since oxidative
stress has been implicated as a contributor to
impaired vascular function, we investigated the
following:</p> <p>Aims: (1) the effects of high glucose exposure <italic>in vitro</italic> (7 – 10 days) on vascular relaxation to acetylcholine
(Ach) and contractility to norepinephrine (NE)
and KCl; (2) if NO-dependent cGMP generation is
affected under these conditions; and (3) aortic redox
status.</p> <p>Methods: Non-diabetic rat tail artery rings were
incubated in normal (5mM) (control NG) or high
(20mM) glucose buffer (control HG). Vascular responses
to Ach, NE and KCl were compared to
those of streptozotocin (SZ) diabetic animals in
the same buffers (diabetic NG, diabetic HG). Ach stimulated
cGMP levels were quantitated as an indirect
assessment of endothelial nitric oxide (NO)
production and oxidative stress evaluated by
measuring vascular glutathione and oxidized
glutathione.</p> <p>Results: Rings from diabetic rats in NG showed
impaired relaxation to Ach (<italic>P</italic> = 0.002) but relaxed
normally, when maintained in HG. Similarly, contractile
responses to NE were attenuated in diabetic
rings in NG but similar to controls in HG. HG
markedly augmented maximal contraction to KCl
compared to control and diabetic vessels in NG
(<italic>P</italic> &lt; 0.0001). Diabetic vessels in a hyperosmolar, but
normoglycemic, milieu respond like those in HG.
<italic>in vitro</italic>, HG for 2 hours changed neither relaxation
nor contractile responses to NE and KCl in control
rings. Basal cGMP levels were lower in aortae
from diabetic animals pre-incubated in NG than in
HG/LG or in control rings in NG (<italic>P</italic> &lt; 0.05). cGMP
responses to Ach were exaggerated in diabetic vessels
in HG (<italic>P</italic> = 0.035 <italic>vs</italic>. control NG, <italic>P</italic> = 0.043 <italic>vs</italic>.
diabetic NG) but not different between control
and diabetic rings in NG. Vessels from diabetic
animals had lower levels of GISH (<italic>P</italic> &lt; 0.0001) and
higher levels of GSSG (<italic>P</italic> &lt; 0.0001) indicating oxidative
stress.</p> <p>Conclusions: Our data indicate that endothelium dependent relaxation is altered early in the diabetic state and that increased NO responses may compensate for augmented oxidative stress but the lack of effect of short-term exposure of normal vessels to HG suggests that short-term hyperglycemia <italic>per se</italic> does not cause abnormal vascular responses.</p>
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Int J Exp Diabetes Res. 2000; 1(1):69-79