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 L(omega)-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 A(2), carnitine-palmitoyl transferase, and fatty acid desaturase activities. Raised NO (high [Ca(++)]) inversely correlated with increased phospholipase-A(2) and acyl-coenzyme A (CoA) synthetase and decreased fatty acid synthetase and beta-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.
Marra
Carlos A
CA
INIBIOLP Instituto de Investigaciones Bioquímicas de La Plata, CONICET-UNLP, Cátedra de Bioquímica, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina. camarra@atlas.med.unlp.edu.ar
Nella
Julio
J
Manti
Damián
D
de Alaniz
María J T
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D002118:Calcium