Lipid Metabolism in Rats is Modified by Nitric Oxide Availability Through a Ca⁺⁺-Dependent Mechanism

We studied lipid metabolism and the antioxidant defense system in plasma and liver of rats fed diets supplemented with Lω-nitro-L-arginine methyl ester (L-NAME), isosorbide dinitrate (DIS), L-arginine (Arg), or the associations of these drugs. Liver hydroperoxide and thiobarbituric-acid-reactive substance (TBARS) levels were decreased by Arg and increased by L-NAME or DIS treatments. Oxidized glutathione and conjugated dienes were increased by DIS. Nitrate + nitrite levels and serum calcium ([Ca⁺⁺]) were incremented by Arg or DIS and reduced by L-NAME. Superoxide dismutase and catalase activities decreased under Arg treatment, while L-NAME or DIS caused stimulation. Liver high-density lipoprotein (HDL) cholesterol was increased by DIS or NAME (alone or associated with Arg). Free fatty acids and neutral and polar lipids were increased by Arg, L-NAME, and DIS. However, predominating phospholipid synthesis increased the neutral/polar ratio. Decreased levels of nitric oxide (NO) (low [Ca⁺⁺]) was directly associated with increased fatty acid synthetase, decreased phospholipase A₂, carnitine-palmitoyl transferase, and fatty acid desaturase activities. Raised NO (high [Ca⁺⁺]) inversely correlated with increased phospholipase-A₂ and acyl-coenzyme A (CoA) synthetase and decreased fatty acid synthetase and β-oxidation rate. Arg or DIS produced changes that were partially reverted by association with L-NAME. Based on these observations, prolonged therapeutical approaches using drugs that modify NO availability should be carefully considered.Instituto de Investigaciones Bioquímicas de La Plat