Nitric oxide in atherosclerosis.

*NO is produced endogenously from L-arginine by NOSs. Among its multiple activities, the homeostatic control of the vascular endothelium is crucial for atherosclerosis, a pathogenic condition connected with elevated levels of LDL, the main plasma cholesterol carrier. Oxidised LDL is proatheromatic, and toxic peroxidation products contribute to further endothelial damage. *NO controls vascular tone, inhibits LDL oxidation and has hypocholesterolaemic activity. This review is referred to the chemistry, biology and role of *NO on atherosclerosis and its treatment by *NO donors or modulators.

Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity.

In this investigation, we study the synthesis and the evaluation of antioxidant and hypocholesterolemic activity of a number of 2-biphenylyl morpholine derivatives, which are structurally similar to some substituted morpholines possessing antioxidant activity, as well as to hypocholesterolemic 3-biaryl-quinuclidines. The novel derivatives are found to inhibit the ferrous/ascorbate induced lipid peroxidation of microsomal membrane lipids, the most potent derivative, 2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol (compound 7), having an IC(50) value of 250 microM. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound (7) decreases total cholesterol, low density lipoprotein, and triglycerides in plasma of Triton WR-1339 induced hyperlipidemic rats by 54%, 51%, and 49%, respectively, at 28 micromol/kg (ip). The above results indicate that the new molecules may be proven useful as leads for the design of novel compounds as potentially antiatherogenic factors.

Cytochrome P450 modification by a new oxazine derivative with hypolipidemic activity.

Plasma lipoprotein levels, related to atheromatosis, are influenced by liver function. Microsomal enzyme inducers are reported to modify serum lipoproteins and triglycerides. In this study, the effects of subchronic and acute treatment of rats with 3-(4-biphenyl)-3-n-propoxy-octahydro-1,4-pyrido[2,1-c]oxazine, a novel compound with hypolipidemic and antioxidant activities, on rat hepatic microsomal protein and total cytochrome P450, as well as on p-nitrophenol hydroxylase (CYP2E) and erythromycin N-demethylase (CYP3A) activities are examined. The subchronic treatment had no significant effect on liver weight, microsomal protein and total cytochrome P450. The acute administration lowered considerably cytochrome P450 content. The metabolic activities of CYP2E1 and CYP3A1/2 were not altered by the subchronic treatment, but were notably decreased after the single administration of 3-(4-biphenyl)-3-n-propoxy-octahydro-1,4-pyrido[2,1-c]oxazine. The inhibition of drug metabolism by 3-(4-biphenyl)-3-n-propoxy-octahydro-1,4-pyrido[2,1-c]oxazine cannot be completely correlated with the modification of plasma cholesterol, triglycerides and LDL cholesterol, although published data connect microsomal enzyme induction with a decrease of these parameters. This discrepancy could be attributed to the different biochemical events involved in enzyme induction and inhibition.