Signaling pathways modulated by fish oil in salt-sensitive hypertension

Abstract

Diaz Encarnacion MM, Warner GM, Gray CE, Cheng J, Keryakos HK, Nath KA, Grande JP. Signaling pathways modulated by fish oil in salt-sensitive hypertension. Am J Physiol Renal Physiol 294: F1323-F1335, 2008. First published April 2, 2008 doi:10.1152/ajprenal.00401.2007.-Although many studies have indicated that fish oil (FO) improves cardiovascular risk factors and reduces histopathological manifestations of injury in experimental renal injury models, potential mechanisms underlying this protective effect have not been adequately defined. The objective of this study was to identify potential signaling pathways that confer protection in the Dahl rat model of salt-sensitive hypertension. Male Dahl saltsensitive rats (n ϭ 10/group) were provided with formulated diets containing 8% NaCl, 20% protein, and 25% FO or 25% corn oil (CO) for 28 days. FO reduced blood pressure (Ϫ11% at 4 wk; P Ͻ 0.05), urine protein excretion (Ϫ45% at 4 wk; P Ͻ 0.05), plasma cholesterol and triglyceride levels (Ϫ54%, P Ͻ 0.001; and Ϫ58%, P Ͻ 0.05), and histopathological manifestations of renal injury, including vascular hypertrophy, segmental and global glomerular sclerosis, interstitial fibrosis, and tubular atrophy. Interstitial inflammation was significantly reduced by FO (Ϫ32%; P Ͻ 0.001), as assessed by quantitative analysis of ED1-positive cells in sections of the renal cortex. FO reduced tubulointerstitial proliferative activity, as assessed by Western blot analysis of cortical homogenates for PCNA (Ϫ51%; P Ͻ 0.01) and quantitative analysis of Mib-1-stained sections of the renal cortex (Ϫ42%; P Ͻ 0.001). Decreased proliferative activity was associated with reduced phospho-ERK expression (Ϫ37%; P Ͻ 0.005) and NF-B activation (Ϫ42%; P Ͻ 0.05). FO reduced cyclooxygenase (COX)-2 expression (Ϫ63%; P Ͻ 0.01) and membrane translocation of the NADPH oxidase subunits p47 phox and p67 phox (Ϫ26 and Ϫ34%; P Ͻ 0.05). We propose that FO ameliorates renal injury in Dahl salt-sensitive rats through the inhibition of ERK, decreased NF-B activation, inhibition of COX-2 expression, and decreased NADPH oxidase activation.fibrosis; glomerulosclerosis; docosahexaenoic acid; eicosapentaenoic acid; rat HYPERTENSIVE NEPHROSCLEROSIS is the second most common cause of end-stage renal disease in the United States (98). Over 70% of the 5.6 million individuals in the United States with elevated serum creatinine levels are hypertensive (16). The risk of end-stage renal disease is directly related to the degree of blood pressure elevation. Hypertension, which occurs in as many as 43 million individuals, is clearly a multifactorial disorder resulting from a variety of environmental and genetic factors. Of the environmental factors, excess dietary salt intake appears to be one of the most important (93, 103). Of note, salt sensitivity is an independent cardiovascular risk factor in patients with hypertension (69).Given the prevalence of hypertension, nontoxic, easily tolerated therapeutic agents that complement standard antihypertensive therapy may play a critical ...

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