Profile of Endothelin Isopeptides and Markers of Oxidative Stress Alongside the Onset of Streptozotocin-Type I Diabetes in Rats

Type I diabetes is associated with vascular endothelial abnormalities. Vasoactive mediators such as endothelins and reactive oxygen species are modulated in diabetic patients. We studied the hemodynamic profile and the release of mediators alongside the onset of streptozotocin-induced type I diabetes in rats. Arterial plasma samples were collected from chronically instrumented, unrestrained and conscious normotensive versus streptozotocin-diabetic rats. Streptozotocin-diabetic rats developed severe hypoinsulinemia and subsequent hyperglycemia within 5 days. Mean arterial blood pressure and heart rate decreased from 107 to 87 mmHg (19%) and from 386 to 282 beats per minute (bpm) (27%), respectively over 21 days. On day 20 post-streptozotocin administration, markers of oxidative stress (reactive oxygen species: hydrogen peroxide, total peroxides) and related vasodilatory nitric oxide metabolites, increased. Plasma concentrations of atrial natriuretic peptide were not affected, while vasocontractile endothelin-1 and big endothelin-1 increased in streptozotocindiabetic rats versus chronically instrumented, unrestrained and conscious normotensive rats. In addition, the ratios of endothelin-1 : big endothelin-1 and nitric oxide : endothelin-1 were increased. The depressed hemodynamic profile may result from an imbalance between vasocontracting and relaxing factors. Their interactions with reactive oxygen species may affect vascular tone and lead to vascular complications prevalent in this pathological condition. Defining the complex regulation and roles of these factors merits further investigations, especially in the later endstages of vascular complications, because the development of these complications is linked to the duration of the diabetic state.