Lipid metabolism and renal protection by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.
We investigated the role of lipid metabolism in renal protection by chronic cicletanine treatment in Dahl salt-sensitive (Dahl S) rats with salt-induced hypertension. Forty-four 6-week old Dahl S rats were divided into four groups: (1) low-salt (0.3% NaCl) control group: (2) high-salt (4% NaCl) control group; (3) low-dose (10 mg/kg/day) cicletanine (CICL)-treated group given a high-salt diet; and (4) high-dose (30 mg/kg/day) cicletanine-treated group given a high-salt diet. The rats were treated for 6 weeks; blood pressure was measured by the tail-cuff method. Cicletanine significantly reduced the systolic blood pressure in a dose-dependent manner (223 mmHg in the high-salt controls vs 195 mmHg in the high-dose, high-salt group, p < 0.01). Cicletanine treatment did not affect plasma concentration of total cholesterol or triglyceride or free fatty acid; in contrast, it significantly decreased low-density lipoprotein (LDL) cholesterol and increased high-density lipoprotein (HDL) cholesterol. Morphological examination demonstrated that glomerulosclerosis in the kidney was significantly improved by 15% with high-dose cicletanine (p < 0.01). Multivariate analysis revealed that glomerular sclerosis was determined independently by LDL cholesterol levels and arterial injury score, but not by total cholesterol or HDL cholesterol levels or blood pressures. LDL cholesterol was also an independent predictor of urinary excretion of protein. Thus, it is suggested that cicletanine treatment lowers the levels of LDL cholesterol in Dahl salt-sensitive rats, and that besides blood pressure reduction, this decrease in LDL cholesterol level contributes, in part, to regression of glomerular injury in salt-induced hypertension.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Hirawa
N
N
Kawabata
Y
Y
Akie
Y
Y
Ichikawa
A
A
Funahashi
N
N
Goto
A
A
Omata
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D006978:Hypertension, Renovascular / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D050356:Lipid Metabolism; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D017673:Sodium Chloride, Dietary
D000959:Antihypertensive Agents; D011725:Pyridines; D017673:Sodium Chloride, Dietary; C038068:cicletanine