Chronic consumption of a high-salt diet causes hypertension (HTN) and renal injury in Dahl salt-sensitive (DSS), but not salt-resistant (DSR) rats. These events are, in part, mediated by oxidative stress and inflammation in the kidney and cardiovascular tissues. Local activation of AT1 receptor plays an important role in the pathogenesis of oxidative stress and inflammation in hypertensive disorders. However, systemic renin-angiotensin system is typically depressed in salt-sensitive HTN. It is of note that circulating and tissue renin-angiotensin systems operate independently. Since renal tissue angiotensinogen is reportedly elevated in hypertensive DSS rats, we hypothesized that differential response to high-salt diet in DSS versus DSR rats may be related to dysregulations of intrarenal AT1 receptor and factors involved in inflammation and reactive oxygen species production. Subgroups of DSS and DSR rats were fed a high-salt (8% NaCl) or low-salt (0.03% NaCl) diet for 2 weeks. DSS rats consuming a regular diet exhibited significant increases in AT1 receptor and COX-2 abundance in the kidney. High-salt intake resulted in marked HTN, proteinuria, and up-regulations of P22phox, MCP-1, and PAI-1, as well as further rises in AT1 receptor and COX-2 abundance in the DSS but not the DSR rat kidneys. Among animals fed a low-salt diet, glutathione peroxidase (GPX) was significantly lower in the DSS compared with DSR kidneys. Consumption of a high-salt diet raised kidney GPX in DSR but not DSS rats and lowered kidney CuZn SOD in DSS rats. Thus, high-salt intake results in up-regulations of AT1 receptor, COX-2, NAD(P)H oxidase, MCP-1, and PAI-1 and down-regulations of key antioxidant enzymes, GPX and CuZn SOD, in DSS rats. These events can contribute to oxidative stress, inflammation, and tissue damage in the DSS kidney.
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