Expression of Vascular Endothelial Growth Factor has a Regulatory Role in Gingival Venules in Experimental Diabetes.

Abstract

BACKGROUND: In the present study we intended to examine the possible localization and role of vascular endothelial growth factor receptor type 2 (VEGFR2) in the regulation of gingival venules in a rat model of experimental diabetes. METHODS: Six weeks after streptozotocin premedication, Wistar male rats presenting blood-sugar levels above 20 mmol/L were selected for investigation. VEGFR2 antagonist ZM323881 (20 mug/mL) was dripped onto the gingiva between the lower incisors. Changes in diameter of the selected gingival venule were measured by vital microscopy combined with digital photography at specified times. Immunohistochemical staining was used to localize VEGFR2. For controls, the same protocol was used applying animals with healthy gingiva. RESULTS: There was a significant difference between the baseline venule diameter of the diabetic and the control group (47 +/- 1 microm and 28 +/- 2 microm, respectively). After 15, 30 and 60 minutes of local application of ZM323881, significant vasoconstriction was observed in the venules of diabetic rats, as compared to the baseline (81.4 +/- 4.6%; 81.8 +/- 4.4%; 80.6 +/- 5.1%, respectively). The control group showed no change in the venule diameter. The immunohistochemical analysis showed significantly increased VEGFR2 expression in the mast cells along the venules in the diabetic group whereas mast cells were rarely found in the control group. CONCLUSIONS: Our findings suggest that VEGF expression is increased in gingiva in experimentally induced diabetes. After VEGFR2 activation, the mast cell-derived vasodilatory and inflammatory mediators may markedly contribute to the concomitant changes in the microcirculation.