Streptozotocin-induced diabetes in rats alters endothelin-1 peptide content, mRNA levels, and receptor binding in blood vessels, suggesting an impaired paracrine effect on vascular smooth muscle that is reversible with insulin.
OBJECTIVE: This study was to examine the effect of streptozotocin-induced diabetes on endothelin-1 and its receptors in the mesenteric artery and in the thoracic aorta. METHODS: Diabetes was induced in SD rats by streptozotocin. Insulin was given subcutaneously. Endothelin-1 levels in the plasma, thoracic aorta and mesenteric artery were measured using radioimmunoassay. The Bmax and Kd values of endothelin-1 receptors in the mesenteric artery and in the thoracic aorta were analyzed using Scatchard plot analysis. Preproendothelin mRNA levels were examined using RT-PCR. RESULTS: Endothelin-1 levels in the mesenteric artery (83.6 +/- 6.9 pg/mg protein) and in the thoracic aorta (73.9 +/- 8.2 pg/mg protein) increased in 2 week diabetic rats compared with both control (51.8 +/- 5.3, 46.3 +/- 5.9 pg/mg protein) and insulin treated rats (65.6 +/- 8.1, 48.1 +/- 4.2 pg/mg protein) but not in 4 week diabetic rats. There was no change in plasma endothelin-1 levels in these diabetic rats. The RT-PCR results indicated that preproendothelin mRNA levels in the mesenteric artery (0.38 +/- 0.02 vs 0.52 +/- 0.05 units) and in the thoracic aorta (0.45 +/- 0.06 vs 0.62 +/- 0.03 units) decreased in 4 week diabetic rats but not in 2 week diabetic rats. A significant increase in Kd and Bmax of endothelin receptors in the mesenteric artery and in the thoracic aorta was observed in both 2 week (about 70%) and 4 week (80-85%) diabetic rats. Insulin replacement reversed the effects of diabetes on endothelin-1 peptide contents, preproendothelin mRNA levels and the binding activity in the blood vessels. CONCLUSION: Increased endothelin peptide content with no change in mRNA or decreased mRNA levels with no change in peptide content together with increased receptor binding sites and affinities might imply a decrease in endothelin release and therefore an impaired paracrine effect of endothelin on vascular smooth muscles in these STZ-diabetic rats.
Shengjun Wu (1998) studied this question.