This work was designed to determine in vivo the influence of the metabolic
control of streptozotocin-induced diabetic rats, measured by the levels of
hemoglobin glycosylation in blood (HbA(1c)) in developing vascular endothel
ial dysfunction. For this, the endothelium-derived vasoactive responses wer
e studied using the technique of the anaesthetized aufoperfused rat, analyz
ing the responsets to acetylcholine in non-diabetic and diabetic rats with
different degree of metabolic control (four groups with HbA(1c) levels of 5
.5-7.4%, 7.5-9.4%,9.5-12%, and >12% respectively). When administered over a
noradrenaline-induced vasopressor tone, acetylcholine (0.25, 0.75, 2.5, 7.
5 and 25 mu g/kg) induced in all rat groups dose dose-dependent vasodilatat
ory responses, both reducing mean arterial pressure and perfusion pressure
of the left hindlimb. These responses were similar in non-diabetic and in d
iabetic rats with good metabolic control (HbA(1c) of 5.5-7.4%), while diabe
tic rats with levels of HbA(1c) higher than 7.5% showed significantly lower
vasodilatatory responses to acetylcholine. In untreated diabetic rats, the
relaxant responses evoked by the nitric oxide donor sodium nitroprusside w
ere analogously impaired. The results indicate that the endothelial dysfunc
tion associated to diabetes is closely related to the level of metabolic co
ntrol of the disease. Therefore, if is possible to establish a threshold fo
r developing endothelium impairment from percentages of HbA(1c) higher than
7.5%.