Albuminuria, expression of nicotinamide adenine dinucleotide phosphate oxidase and monocyte chemoattractant protein-1 in the renal tubules of hypertensive Dahl salt-sensitive rats.
In chronic renal diseases, experimental and human data suggest that excess albumin filtered through the glomerular capillary barrier is over-reabsorbed by proximal tubular cells, thereby activating these cells and upregulating the expression of chemokines. On the other hand, a high-salt diet has been shown to induce proteinuria in hypertensive Dahl salt-sensitive (DSS) rats, accompanied with the expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the kidney. In the current study, we therefore examined albuminuria and the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) in the renal tubular cells in hypertensive DSS rats, as well as the effects of the antioxidant N-acetylcysteine (NAC) on each of these parameters. DSS rats were fed a normal-salt diet (0.24% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus NAC supplementation (15 mg/mL drinking water) for 4 weeks. The high-salt diet provoked an increase in glomerular injuries accompanied with albuminuria and in urinary H2O2 and MCP-1 excretion. Immunohistochemical analysis showed the prominent expression of MCP-1 in the dilated tubular cells, where the NADPH oxidase subunit p47phox was also expressed. The current results suggest that albuminuria caused expression of NADPH oxidase and MCP-1 in the dilated renal tubules, resulting in interstitial inflammation and migration of mononuclear cells in DSS rats, because blockade of albuminuria by NAC counteracted the p47phox and MCP-1 expression.
Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Japan.
Shigemoto
S
Fujii
Ling
L
Zhang
Hiroaki
H
Kosaka
D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D015870:Gene Expression; D006973:Hypertension / Q000378:metabolism*; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl
D018932:Chemokine CCL2; D019255:NADPH Oxidases