Signaling pathways modulated by fish oil in salt-sensitive hypertension.
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 salt-sensitive rats (n = 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 (-11% at 4 wk; P < 0.05), urine protein excretion (-45% at 4 wk; P < 0.05), plasma cholesterol and triglyceride levels (-54%, P < 0.001; and -58%, P < 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 (-32%; P < 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 (-51%; P < 0.01) and quantitative analysis of Mib-1-stained sections of the renal cortex (-42%; P < 0.001). Decreased proliferative activity was associated with reduced phospho-ERK expression (-37%; P < 0.005) and NF-kappaB activation (-42%; P < 0.05). FO reduced cyclooxygenase (COX)-2 expression (-63%; P < 0.01) and membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox) (-26 and -34%; P < 0.05). We propose that FO ameliorates renal injury in Dahl salt-sensitive rats through the inhibition of ERK, decreased NF-kappaB activation, inhibition of COX-2 expression, and decreased NADPH oxidase activation.
Diaz Encarnacion
Montserrat M
MM
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Warner
Gina M
GM
Gray
Catherine E
CE
Cheng
Jingfei
J
Keryakos
Hesham K H
HK
Nath
Karl A
KA
Grande
Joseph P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005395:Fish Oils / Q000494:pharmacology*; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020303:Rats, Inbred Dahl; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D004041:Dietary Fats; D005395:Fish Oils; D016328:NF-kappa B; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D003314:Corn Oil; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1