Age-related changes in cholesterol and bile-acid metabolism in spontaneously hypertensive rats

Age-related changes in serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoproteins, biliary secretion of cholesterol, phospholipids and bile acids, fecal excretion of sterols and bile acids, and the pool size of bile acids were examined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKR). SHR showed distinct age- and sex-related changes when young and marked aged-rat hypercholesterolemia after 1 yr of age. (1) Cholesterol shifted from blood to the liver between 10 and 20 wk only in male SHR and not at all in WKR. (2) Serum lipoprotein percentages changes; α-lipoprotein decreased, pre-β-lipoprotein increased, but β-lipoprotein did not change. These changes appeared only in male SHR and after 13 to 15 wk of age. (3) Liver enlargement in SHR, although not detected at 5 to 6 wk, progressed more rapidly than in WKR, giving values almost double those in WKR after 13 to 15 wk. Liver enlargement in female SHR was much less than in the male. (4) Bile flow, biliary secretion, and the pool size of bile acids increased. However, when expressed on the basis of liver weight, these values were similar to those in WKR, suggesting that the increases were caused by the hepatomegaly. (5) Differences appeared in the bile acid composition. A large amount of β-muricholic acid was present in SHR of both sexes and the cholic acid percentage was low in male SHR. (6) Changes were observed in fecal bile acid excretion. Since the daily amounts in male SHR were similar to those in WKR, the hepatic synthesis activity (mg per day per 10 g liver) in male SHR was almost half that in WKR at all ages.