We determined the effect of a short-term
angiotensin II signaling blockade on
vascular endothelial growth factor (
VEGF), soluble
intercellular adhesion molecule-1 (sICAM-1),
nitric oxide (NO), and
malondialdehyde (MDA) (index of lipid peroxidation) levels in the systemic circulation and on
peroxynitrite generation and insulitis development in the
streptozotocin (STZ) diabetic rats' pancreas. Diabetes was induced in Wistar rats by intraperitoneal STZ injection. Diabetic rats were treated for 1 week with
losartan (20 mg/kg/
body weight/day in the
drinking water), and pancreas and blood were collected for histochemical, immunohistochemical, and biochemical studies. Diabetic rats showed greater
VEGF, sICAM-1, NO, and MDA levels, a high score of insulitis, increased
nitrotyrosine staining, and markedly reduced pancreatic
insulin content when compared with controls.
Losartan treatment suppressed the excessive NO and lipid peroxidation production systemically without restoring them to that of healthy subjects and reduced
VEGF levels while leaving sICAM-1 levels unchanged. The insulitis score and
nitrotyrosine staining were reduced, whereas the pancreatic islets and the beta-cell area were increased significantly in the treated group, indicating the reduction of
inflammation and nitrosative stress and an early regeneration of beta-cell mass in the pancreas. Conclusively, in the STZ diabetic rat model, even a short-term
losartan treatment improves oxidative and nitrosative stress systemically and locally, improving the islets' environment and accelerating beta-cell regeneration.