Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats.
Recently, hyperlipidemia as well as hypertension has been observed in Dahl salt-sensitive (S) rats. In this study, to investigate whether the lipid abnormality is involved in the renal injury of Dahl S rats, we examined the effect of vitamin E on glomerular sclerosis, as vitamin E is an inhibitor of lipid oxidation. Dahl S rats were given a high salt diet (8% NaCl) containing either normal vitamin E (2 mg/100 g) or high vitamin E (50 mg/100 g) for 4 weeks. Dahl salt-resistant (R) rats were given a high salt and normal vitamin E diet. The blood pressure in the Dahl rats increased and was not suppressed by the vitamin E supplement. Serum cholesterol and triglycerides in Dahl S rats were higher than in Dahl R rats at both 0 and 4 weeks. Vitamin E lowered the serum cholesterol level in Dahl S rats at 4 weeks (126 +/- 5 v 150 +/- 12 mg/dL, P < .01). Urinary protein excretion and serum creatinine increased in Dahl S rats, and vitamin E inhibited the increases significantly (urinary protein, 70.7 +/- 0.9 v 178.0 +/- 8.8 mg/day, P < .01; serum creatinine, 0.45 +/- 0.02 v 0.63 +/- 0.05 mg/dL, P < .01). Serum lipid peroxide (LPO) was higher in Dahl S rats than in Dahl R rats, and vitamin E lowered LPO in Dahl S rats (2.10 +/- 0.03 v 2.70 +/- 0.04 nmol/mL, P < .01). In the histologic study, sclerosing score (SS) of glomeruli, which represents the degree of glomerulosclerosis semiquantitatively, was higher in Dahl S rats than in Dahl R rats. Vitamin E lowered SS (114 +/- 3 v 157 +/- 6, P < .01) and ameliorated arterial injuries such as medial thickness with partial necrosis and severe fibrinoid proliferation with inflammatory cell infiltration. In all rats, SS was strongly correlated with urinary protein (r = 0.93, P < .01), serum cholesterol (r = 0.86, P < .01), and serum LPO (r = 0.89, P < .01). These results suggest that the renal injury in Dahl S rats is caused not only by hypertension but also by hyperlipidemia. Therefore, vitamin E might ameliorate the renal damage by inhibiting the oxidation of lipids.
Atarashi
K
K
2nd Department of Internal Medicine, The University of Tokyo, Bunkyo-ku, Japan.
Ishiyama
A
A
Takagi
M
M
Minami
M
M
Kimura
K
K
Goto
A
A
Omata
M
M
D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D009336:Necrosis; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains / Q000097:blood / Q000235:genetics / Q000652:urine; D012965:Sodium Chloride / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D008054:Lipid Peroxides; D008055:Lipids; D014810:Vitamin E; D012965:Sodium Chloride