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The authors investigated the effect of pravastatin and fluvastatin on paraoxonase 1 (PON1) activity in plasma, liver, heart, and kidney, as well as on plasma platelet activating factor acetylhydrolase (PAF-AH) in the rat. The animals received pravastatin at doses of 4 and 40 mg/kg/d or fluvastatin at doses of 2 or 20 mg/kg/d for 3 weeks. Fluvastatin (20 mg/kg/d) reduced plasma PON1 activity toward paraoxon and phenyl acetate by 23.6% and 17.4%, respectively. The lower dose of this drug as well as both doses of pravastatin had no effect on plasma PON1. PON1 activity toward paraoxon in the liver of rats treated with 20 mg/kg/d fluvastatin was 27.5% lower than in the control group, and the activity toward phenyl acetate was reduced by 25.4% and 35.9% in rats receiving 2 and 20 mg/kg/d of this drug, respectively. Fluvastatin at 2 and 20 mg/kg/d also decreased cardiac PON1 by 31.3% and 27.3%, respectively. Both statins reduced PON1 activity in the renal cortex and medulla. Statins had no effect on plasma PAF-AH. It is concluded that fluvastatin reduces PON1 activity more efficiently than does pravastatin. Reducing effect on PON1 may negatively modulate atheroprotective potential of statins and may contribute to differences in antiatherosclerotic properties of different drugs in this group.

BELTOWSKI, JERZY, GRAŻ YNA WÓ JCICKA, AND ANNA JAMROZ. Stimulatory effect of leptin of nitric oxide production is impaired in dietary-induced obesity. Obes Res. 2003;11:1571-1580. Objective: We investigated the effect of leptin on nitric oxide production in lean and rats made obese by a highcalorie diet. Research Methods and Procedures:The animals were placed in metabolic cages, and urine was collected in 2-hour periods after leptin (1 mg/kg intraperintoneally) or vehicle administration. Blood was obtained 0.5, 1, 2, 4, or 6 hours after injection. Results: Leptin had no effect on systolic blood pressure in either lean or obese animals. Plasma concentration of NO metabolites (nitrites ϩ nitrates, NO x ) increased in lean rats by 31.5%, 58.0%, and 27.9% at 1, 2, and 4 hours after leptin injection, respectively. In the obese group, plasma NO x increased only at 2 hours (ϩ36.5%). Leptin increased urinary NO x excretion by 31.8% in the first 2-hour period after injection in lean but not in obese rats. In lean animals, leptin elevated plasma cyclic 3Ј,5Ј-guanosine monophosphate (cGMP) at 1, 2, and 4 hours by 35.3%, 96.3%, and 57.3%, respectively. In the obese group, plasma cGMP was higher only at 2 and 4 hours (ϩ44.6% and ϩ32.1%, respectively). Urinary excretion of cGMP increased in lean animals by 67.1% in the first period and by 50.4% in the second period. In the obese group, leptin induced a 53.9% increase in urinary cGMP excretion only in the first 2-hour period. Discussion: The stimulatory effect of leptin on NO production is impaired in dietary-induced obesity; however, leptin does not increase blood pressure in obese animals, suggesting that other NO-independent depressor mechanisms are stimulated.

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