Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery was examined in miniature pigs. A diffuse intimal thickening was observed in vehicle-treated controls 6 weeks after balloon catheterization. The histologic features of the intimal thickening resembled those of early atherosclerotic lesions and restenosis after percutaneous transluminal coronary angioplasty (PTCA). Nilvadipine given in a daily dose of 10 mg/kg (subcutaneously, s.c.) for 6 weeks significantly inhibited intimal thickening. The ratio of the cross-sectional area of the intima to the cross-sectional area of the media was significantly reduced by 62% in nilvadipine-treated animals. These results suggest that nilvadipine may prevent or exert beneficial effects on coronary arterial injuries such as atherosclerosis and restenosis after PTCA.
 ...
PMID:Effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery in miniature pigs. 128 Jul 34

1. Nilvadipine (FK 235, FR 34235) suppressed ischemia (20 min)-reflow (20 min)-induced paw edema of mice (ED30:0.4 mg/kg i.v. and 2 mg/kg p.o.). Other calcium entry blockers of dihydropyridine-type also suppressed the edema, but 30-fold higher doses were required. 2. Oral dosing of nilvadipine suppressed carrageenan-induced paw edema (ED30:15 mg/kg in rats and 20 mg/kg in mice) at a potency corresponding to that of an anti-inflammatory drug, ibuprofen. Nifedipine, nicardipine and nimodipine resulted in a suppression of 30% only with 100 mg/kg oral dosing in rats. Nitrendipine, diltiazem and verapamil were without effect. 3. Nilvadipine inhibited superoxide radical (O-2production from xanthine oxidase (XOD) both with lactate dehydrogenase + NADH method and cytochrome c method (IC50:90 and 100 micrograms/ml, respectively). Nifedipine and nicardipine showed some inhibition, but the other calcium entry blockers failed to inhibit significantly even at 320 micrograms/ml. As uric acid formation was not reduced by the tested drugs, the inhibitory action might be due to their O-2scavenging effects. 4. Superoxide production of neutrophils from casein-induced peritoneal fluid in rats was most strongly inhibited by nilvadipine when the cells were stimulated by a calcium ionophore, A23187 (IC50:4 micrograms/ml). Inhibition by this drug when stimulated by f-methonyl-leucyl-phenylalanine and phorbol myristate acetate was less effective (IC50:20 and 30 micrograms/ml, respectively). Nifedipine and nicardipine inhibited neutrophil O-2production at higher concentrations (30-200 micrograms/ml) with all stimulants. Inhibitory actions by other drugs were weak. 5. Triggering of atherosclerosis depends largely on the oxidative stress on blood vessels after recently established concept.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition by nilvadipine of ischemic and carrageenan paw edema as well as of superoxide radical production from neutrophils and xanthine oxidase. 165 7

Nilvadipine and other calcium antagonists were studied for their effect on 1-alpha-hydroxyvitamin D3 (1 - alpha (OH)D3)-induced aortic calcium deposition in rats. The animals were treated orally with 1-alpha (OH)D3 (10 micrograms/kg) for 2 weeks. Calcium antagonists were given orally twice a day during the same period. The aortic calcium content in 1-alpha (OH)D3-treated rats increased to about 100 times that in the control. Nilvadipine reduced the aortic calcium deposition dose-dependently, with percent inhibition of 6, 43, 72 and 92%, at doses of 0.1, 1, 10 and 100 mg/kg, respectively. Similar activities were obtained for the other calcium antagonists except diltiazem which had no effect even at the largest dose of 100 mg/kg. According to the ED50 values, nilvadipine (2.2 mg/kg) was more potent than nifedipine (23.2 mg/kg), nicardipine (12.4 mg/kg) and verapamil (32.0 mg/kg). Scanning and transmission electron microscopy showed clear-cut degenerative changes in the endothelial cells after 1-alpha (OH)D3 treatment. Nilvadipine exerted a protective effect against these degenerative changes but not against 1-alpha (OH)D3-induced hypercalcemia. Furthermore, the drug had only minimal effect on in vitro calcification of the aorta. Our findings suggest that nilvadipine inhibits aortic calcification by protecting the aortic wall cells.
Atherosclerosis 1988 Oct
PMID:Protective action of a calcium antagonist, nilvadipine, against aortic calcium deposition--a pathogenic factor in atherosclerosis. 326 72

The antiatherogenic activity of FR34235 (Nilvadipine), a calcium antagonist, was examined in rabbits with carotid arteries sheathed with polyethylene cuffs, and compared with that of nifedipine, verapamil and diltiazem. The drugs were given intramuscularly in daily doses of 0.01-10 mg/kg for 3 weeks, starting on the day of cuff-placement. FR34235 dose-dependently inhibited the cuff-induced intimal thickening, and was more potent than the other calcium antagonists, whose order of potency was nifedipine, diltiazem and verapamil. In an in vitro experiment on inhibition of migration of rat aortic smooth muscle cells, using zymosan-activated air pouch exudate as a chemoattractant in modified Boyden chambers, FR34235 was also the most potent among the calcium antagonists tested. The IC50 values were 3.3 X 10(-11) M for FR34235, 1.7 X 10(-10) M for nifedipine, 6.0 X 10(-9) M for verapamil and 2.4 X 10(-7) M for diltiazem. Effects of these drugs on proliferation of rat aortic smooth muscle cells and rabbit platelet aggregation were also examined in vitro. At concentrations less than 10(-5) M, none of the drugs inhibited proliferation of the smooth muscle cells, and only verapamil inhibited collagen-induced platelet aggregation (IC50 = 9.0 X 10(-7) M). It is suggested that FR34235 should be useful for preventing and treating atherosclerosis. Inhibition of smooth muscle cell migration is thought to be its mechanism of antiatherogenic activity.
Atherosclerosis 1987 Apr
PMID:Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery. 360 23

Twelve adults (age 32-61 years) with essential hypertension were recruited from the outpatient clinics of National Defense Medical College hospital to serve as subjects in the present study. They were treated with nilvadipine, a Ca-antagonist, 4 mg b.i.d. for 4 weeks. LDL samples were isolated by ultracentrifugation at the beginning (week 0) and at the end (week 4) of the treatment regimen. The formation of conjugated dienes was measured by incubating 100 micrograms of LDL protein with 2 mumol CuSO4 in 2 ml phosphate buffered saline (PBS). There were no significant differences between lipids levels, composition and anti-oxidant levels of LDL at weeks 0 and 4. The lag time of LDL oxidation was 71.1 +/- 11.3 min at week 0 and 81.3 +/- 13.2 min at week 4 (p < 0.05). In vitro studies of LDL oxidation, evaluated by thiobarbituric acid reactive substances (TBARS) and by agarose electrophoretic mobility, indicated that nilvadipine inhibited the oxidative modification of LDL while amlodipine, used as control, did not. Nilvadipine, a lipophilic Ca-antagonist, significantly prolonged the lag time of conjugated diene formation of LDL by 12.6% but amlodipine, a hydrophilic Ca-antagonist, had no major effect on LDL oxidation. These results suggest that Ca-antagonists are effective for the prevention of atherosclerosis but the effect is dependent upon the lipophilicity of the drugs.
 ...
PMID:Effects of Ca-antagonists on oxidative susceptibility of low density lipoprotein (LDL). 758 10