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Feeding Rats the Nitric Oxide Synthase Inhibitor, L-NNitroarginine, Elevates Serum Triglyceride and Cholesterol and Lowers Hepatic Fatty Acid Oxidation¹

Department of Applied Biochemistry, Faculty of Applied Biological Science, Hiroshima University, Higashi-Hiroshima 739, Japan ^* Development, Health Care, Kissei Pharmaceutical Company, Matsumoto 399, Japan

This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-Nnitroarginine (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 cholesterol 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 elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results 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.

KEY WORDS: • L-Nnitroarginine • L-arginine • nitric oxide • lipid metabolism • rats

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

² To whom correspondence and reprint requests should be addressed.

Manuscript received 14 November 1995. Revision accepted 2 July 1996.

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