Histological and Immunohistochemical Study on Nitric Oxide Synthase and Effects of Angiotensin Receptor Blockade in Early Phase of Diabetes in Rat Kidney

Abstract

Hypothesis: Several studies demonstrated that the patho-physiologic and morphologic changes in early diabetic nephropathy were mediated by either an increase or decrease in the nitric oxide (NO) production and/or activity. There are few reports suggesting a relationship between NO and renin-angiotensin system. Objectives: The present study was designed to determine the effects of early diabetic state on NO production and also to assess the protective effects of angiotensin receptor blockers (ARB) on these changes. Material and Methods: Thirty adult male albino rats were included in this study. Twenty were injected with streptozotocin for induction of diabetes. The other ten were injected with the vehicle and served as control. Two days after injection, the diabetic animals were randomly divided into two groups of ten 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 paraffin sections. The sections were stained with H & E, Masson trichrome and PAS reaction. Also, the sections were stained with immunohistochemical stain against endothelium-derived nitric oxide synthase (eNOS). Results: Diabetes induced histological changes in the form of glomerular hypertrophy, increased glomerular matrix, focal areas of tubular atrophy, medullary congestion and slight fibrosis. eNOS immunostaining was present in the control kidney in the golumeruli and the collecting tubules of the medulla. Diabetes induced positive reaction in the proximal and distal convoluted tubules and increased eNOS immunoreactivity in the collecting tubules. Treatment with Valsartan induced improvement of the morphology of the kidney and reduction in the intensity of eNOS immunostaining. Conclusion: NO increases in early diabetic kidney and ARB as Valsartan could be recommended in the prevention of the development of diabetic nephropathy.