Histological and immunohistochemical study of nitric oxide synthase and effects of angiotensin receptor blockade in early phase of diabetes in rat kidney

ABSTRACT

Several studies have demonstrated that the pathophysiological and morphological changes in early diabetic nephropathy were mediated by an increase or decrease in nitric oxide [NO] production and/or activity. There are few reports suggesting a relationship between NO and the renin-angiotensin system. The present study was designed to determine the effects of early diabetic state on NO production and also to assess the possible effects of angiotensin receptor blockers [ARBs] on these changes. Thirty adult male albino rats were included in this study. Twenty were injected with streptozotocin for induction of diabetes. The other 10 were injected with the vehicle and served as control. Two days after injection, the diabetic animals were randomly divided into two groups of 10 animals each. One group was given valsartan as an ARB and the other group received no further treatment. Three weeks later, all animals were sacrificed and the kidneys were processed for obtaining paraffin sections. The sections were stained with H and E, Masson's trichrome, and periodic acid-Schiff. The sections were also stained with an immunohistochemical stain against endothelium-derived nitric oxide synthase [eNOS]. Diabetes induced histological changes in the form of glomerular hypertrophy, increased glomerular matrix, focal areas of tubular atrophy, medullary congestion, and slight fibrosis. Immunostaining was present in the control kidney in the glomeruli and in the collecting tubules of the medulla. Diabetes induced a positive reaction in the proximal and distal convoluted tubules and increased immunoreactivity in the collecting tubules. Treatment with valsartan resulted in an improvement in the morphology of the kidney and a reduction in the intensity of eNOS immunostaining. NO increases in early diabetic kidney and ARB in the form of valsartan could be recommended for preventing the development of diabetic nephropathy