Abstract
Reactive oxygen species (ROS) have been implicated in hypertensive organ damage. However the precise mechanism of ROS-mediated organ damage is not fully understood. We recently demonstrated that up-regulation of NADPH oxidase, which is a superoxide-producing enzyme, was associated with renal injury in hypertensive Dahl salt-sensitive (DS) rats. In the present study we investigated the role of monocyte chemoattractant protein-1 (MCP-1) in renal injury in hypertensive DS rats and the effect of antioxidant treatment on MCP-1 expression. High salt diet (8% NaCl) significantly increased urinary MCP-1 excretion and MCP-1 mRNA expression in kidney in DS rats, associating with urinary hydrogen peroxide excretion and expression of p47phox, which is a subunit of NADPH oxidase. Immunostaining showed strong expression of MCP-1 in damaged renal tubules and the expression of MCP-1 was correlated with macrophage infiltration. Antioxidant N-acetyl-L-cysteine supplement with high salt diet abrogated the increase in MCP-1 expression, macrophage infiltration, and tubular and glomerular lesion in the kidney. These data suggest that ROS-associated MCP-1 expression plays an important role in renal injury in hypertensive DS rats. [Jpn J Physiol 55 Suppl:S93 (2005)]
