Abstract
The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.
Highlights
The imbalance of different vasoactive substances contributes to the development and progression of complications in Diabetes Mellitus (DM)
These results provide evidence that L-Arg administration did not prevent the loss of weight in diabetic animals
These results indicate that L-Arg administration did not correct the levels of blood and urinary glucose in diabetic rats, it partially corrected the value of urinary ketones
Summary
The imbalance of different vasoactive substances contributes to the development and progression of complications in Diabetes Mellitus (DM). Nitric oxide (NO) synthesis is found to be abnormal [1] and several studies have provided evidence involving diabetes as a state of renal NO deficiency [2]. The kidney plays a key role in Arg metabolism and the enzymes that participate in L-Arg synthesis are down-regulated in DM, impairing L-Arg production quite early before any significant structural damage is evident, contributing to the resulting NO deficiency [4]. Serum levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, are increased in both type 1 and type 2 DM, which leads to a decrease in NO production and contributes to diabetic complications such as nephropathy and retinopathy [6]
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