Metabolic control and endothelial dysfunction in diabetic rats

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%.