Hypercholesterolemic Effect in Rats of a Dietary Addition of the Nitric Oxide Synthase Inhibitor, L-N^ωNitroarginine, by Less Synthesis of Bile Acids

概要

論文の詳細を見る
We have previously reported that feeding rats with a diet containing 0.02% L-N^ωnitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, induced hypercholesterolemia. This present study was conducted to examine the underlying mechanism for hypercholesterolemia in rats. In experiment 1,feeding a diet containing 0.02% L-NNA for 5wk elevated the concentration of serum cholesterol and reduced the excretion of fecal bile acids, but did not affect the excretion of fecal neutral sterols. Reduced activity of hepatic cholesterol 7 α-hydroxylase, the rate-limiting enzyme for the biosynthesis of bile acids from cholesterol, was observed in the rats receiving L-NNA. In experiment 2,rats were fed for 5 wk on a diet with or without 0.02% L-NNA that or was not supplemented with 4% L-arginine. The L-NNA treatment elevated the serum concentrations of total cholesterol, free cholesterol and esterified cholesterol, and reduced the activity of hepatic cholesterol 7 α-hydroxylase, serum nitrate (a metabolite of NO) and the ratio of HDL-cholesterol versus serum total cholesterol. These alterations were suppressed by supplementing the L-NNA-containing diet with L-arginine. The results suggest that lower NO production by L-NNA caused hypercholesterolemia by a mechanism involving impaired bile acid synthesis.
社団法人日本農芸化学会の論文
1998-04-23