nitrophenols and Arteriosclerosis

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Aryldialkylphosphatase; Esterases; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nitrophenols; Paraoxon; Peritoneal Dialysis; Phenylacetates; Reference Values; Renal Dialysis

We studied the effects of efonidipine hydrochloride [NZ-105: (+/-)-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2- yl)-4-(3-nitro-phenyl)-3-pyridinecarboxylate hydrochloride ethanol] and nisoldipine on endothelial cell-induced low density lipoprotein (LDL) modification. The modification of LDL by cultured rat endothelial cells was performed by incubating 3 micrograms protein/well LDL with 5 microM CuSO4 for 24 hr at 37 degrees C in the presence of confluent cells. The extent of modification was assayed by measuring the thiobarbituric acid-reactive substances (TBARS). Efonidipine hydrochloride reduced the TBARS level in a dose-dependent manner. At 3 x 10(-7) M, efonidipine hydrochloride showed a significant effect. On the other hand, the significant effect of nisoldipine was observed only at 10(-5) M. Thus the action of efonidipine hydrochloride on the inhibition of LDL-modification was much more potent than that of nisoldipine. As the modification of LDL was thought to play a key role in the initiation and progression of atherosclerosis, efonidipine hydrochloride may be useful against atherosclerosis.

Topics: Animals; Arteriosclerosis; Calcium Channel Blockers; Cells, Cultured; Depression, Chemical; Dihydropyridines; Dose-Response Relationship, Drug; Endothelium; Lipoproteins, LDL; Male; Nisoldipine; Nitrophenols; Organophosphorus Compounds; Rats; Rats, Wistar

We studied the effect of efonidipine hydrochloride [NZ-105:(+-)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl )-3-pyridine-carboxylate hydrochloride ethanol], a newly synthesized dihydropyridine calcium antagonist, on atherosclerosis in 1% cholesterol-fed rabbits. NZ-105 (10, 30 and 100 mg/kg) was orally administered to the animals twice a day for 10 weeks. NZ-105 did not cause any significant change in the plasma lipid levels. The area of atherosclerotic lesion was reduced by 37% (P < 0.05) in the aortic arch and by 54% (P > 0.05) in the thoracic aorta of rabbits administrated 100 mg/kg of NZ-105. The content of cholesterol ester in the aorta was also reduced by 64% (P < 0.05) in the aortic arch and by 73% (P > 0.05) in the thoracic aorta. These results suggest that NZ-105 may suppress the development of atherosclerosis without affecting the plasma lipids.

Topics: Animals; Aorta; Aortic Diseases; Arteriosclerosis; Calcium; Cholesterol; Cholesterol, Dietary; Diet, Atherogenic; Dihydropyridines; Lipids; Nitrophenols; Organophosphorus Compounds; Rabbits

Topics: Animals; Anisoles; Aorta; Arteriosclerosis; Body Weight; Carbon Isotopes; Cholesterol; Dealkylation; Diet, Atherogenic; Enzyme Activation; Histamine H1 Antagonists; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Nitrophenols; Organ Size; Phenobarbital; Phospholipids; Piperazines; Proteins; Rabbits; Testosterone; Time Factors

Topics: 2,4-Dinitrophenol; Arteriosclerosis; Atherosclerosis; Dinitrophenols; Nitrophenols; Thyroxine