FEEDING RATS THE NITRIC-OXIDE SYNTHASE INHIBITOR, L-N(OMEGA)NITROARGININE, ELEVATES SERUM TRIGLYCERIDE AND CHOLESTEROL AND LOWERS HEPATIC FATTY-ACID OXIDATION

This study was conducted to examine whether nitric oxide regulates lip id metabolism. In Experiment 1, rats were fed for 5 wk diets with or w ithout 0.2 g/kg L-N(omega)nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g /kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholester ol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2 , rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA el evated serum concentrations of free fatty acids without affecting thos e of ketone bodies. L-NNA lowered the activity of hepatic carnitine pa lmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydroge nase and fatty acid synthase which are lipogenic enzymes. These result s suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation.