Hepatic Synthesis of Cholesterol in Nephrotic Rats

Abstract

The nephrotic state was induced in 17 male Long-Evans strain rats, 8.12 wks. of age, by intraven. injn. of rabbit anti-rat kidney serum on each of 2 successive days. At 2, 5, and 14 days following the 2nd injns. a group of nephrotic rats and a group of controls were subjected to bile duct cannulation. Bile was collected for 24 hrs. (and also 24-48 hrs. in the 5 day group) and analyzed for total vol., total cholesterol and cholic acid. The control plasma cholesterol and cholic acid concn. was ascertained from each rat preoperatively. The hypercholesterem-ics averaged 136 mg. % at 2 days, 252 mg. % at 5 days and 776 mg. % at 14 days in the nephrotic groups. The controls averaged about 60 mg. %. The plasma cholic acid averaged about 7 mg. % in the nephrotic groups and 2.5 mg. % in the controls. The 24 hr. bile vol. of all nephrotic rats averaged 11.4 ml., that of the 12 controls, 11.9 ml. The avg. 24 hr. biliary content of cholesterol of the nephrotic rats was 1.4 mg., of 1.7 mg. The avg. daily output of cholic acid by the nephrotic rats was 22.6 mg., essentially the same as that of the controls, 23.4 mg. The authors suggest that the hypercholesteremia of the nephrotic rat is neither initiated nor maintained by an accelerated rate of synthesis of cholesterol by the liver since the rate of biliary excretion of cholesterol reflects the rate of liver synthesis of cholesterol.