The present paper describes the effect of six-week oral administration of verapamil and diltiazem (1 mg.kg-1 of weight two times daily in 12 hour intervals) on the content of fatty acids of the serum and myocardium of PHHC rats. A cholesterol diet changes the content of fatty acids of the serum and myocardium of PHHC rats in comparison with control rats without the cholesterol diet. A significant decrease in the content of palmitic acid, a decrease in the content of stearic acid, linoleic acid and arachidonic acid and a significant increase in the content of oleic acid were observed in the serum. Long-term administration of the slow calcium channel blockers produces another decrease in the content of the bound form of arachidonic acid. Changes in the representation of other fatty acids are not marked. Long-term administration of a cholesterol diet produces an increase in the content of palmitic acid and stearic acid and a decrease in the content of oleic acid, linoleic acid and arachidonic acid in the myocardium. Administration of verapamil results in a modification of the above-mentioned changes in all parameters excepting the content of arachidonic acid, the content of which was decreased in an even more marked manner. Administration of diltiazem produced an accumulation of both saturated and mono-unsaturated fatty acids (palmitic, stearic and oleic acids) and produced a significant decrease in the content of linoleic acid and mainly the bound form of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
- MeSH
- diltiazem farmakologie MeSH
- hypercholesterolemie krev metabolismus MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- mastné kyseliny krev metabolismus MeSH
- myokard metabolismus MeSH
- verapamil farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- diltiazem MeSH
- mastné kyseliny MeSH
- verapamil MeSH
The objective of the work was to investigate the effect of calcium blockers--dilthiazem (2 mg.kg-1.day-1), isradipine (2.5 mg.kg-1.day-1) and verapamil (0.25 mg.kg-1.day-1) on the calcium and magnesium content of the rabbit aorta with experimental atherosclerosis induced by a 1% cholesterol diet. In the aorta of rabbits kept on a cholesterol diet the calcium and magnesium content, as compared with a control group on a ordinary diet, increased significantly. In the experimental groups to whom during the eight-week period on the cholesterol diet at regular 12-hour intervals calcium antagonists were administered the calcium and magnesium content of the aorta reached normal levels. The antiatherogenic effect was, however, produced only by verapamil when administered in therapeutic doses.
- MeSH
- aorta chemie MeSH
- arterioskleróza metabolismus MeSH
- blokátory kalciových kanálů farmakologie MeSH
- cholesterol dietní aplikace a dávkování MeSH
- hořčík analýza MeSH
- králíci MeSH
- vápník analýza MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- blokátory kalciových kanálů MeSH
- cholesterol dietní MeSH
- hořčík MeSH
- vápník MeSH
Calcium ions act as intracellular messengers in numerous cellular functions and participate also in the development of the atherosclerotic process. Calcium homeostasis could be an important factor in the development of atherosclerosis. One of the drugs which interferes with calcium homeostasis are calcium channel blockers. A number of studies have investigated the possibility whether these drugs may be also useful for prevention of atherosclerosis. However, other investigators have reported that calcium channel blockers did not suppress the atherosclerotic process. In our work we assumed the direct influence of calcium channel blockers on transendothelial transport mechanisms. Therefore we decided to investigate the influence of verapamil, diltiazem and isradipine on the development of experimental atherosclerosis in rabbits. Verapamil administered twice daily, 0.125 mg per kg s. c., reduced the size of atheromatous plaques in the thoracic aorta and the level of total cholesterol and triglycerides in serum. This above effect was not present after administration of diltiazem in doses of 1.0 mg per kg and isradipine 1.25 mg per kg twice daily subcutaneously. Our conclusion is that the anti-atherosclerotic effect of calcium channel blockers is dose-dependent. It is not clear whether this effect takes place in the plasma compartment and/or in the intracellular compartment.
- MeSH
- blokátory kalciových kanálů farmakologie MeSH
- cévní endotel metabolismus patologie MeSH
- histocytochemie MeSH
- hypercholesterolemie metabolismus patologie MeSH
- králíci MeSH
- metabolismus lipidů * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- blokátory kalciových kanálů MeSH
The aim of the study was to assess the dose dependence of the antiatherogenic effect of verapamil (Isoptin, Lek Ljubljana, Yugoslavia) in rabbits fed 1% cholesterol diet. Verapamil was administered subcutaneously at doses of 0.25, 1 and 2 mg.kg-1/day at 12-hour intervals for 8 weeks. The results indicate verapamil administered s.c. exerts a preventive anti-atherosclerotic effect only in therapeutic doses (0.25 mg.kg-1). The beneficial effect of low-dose verapamil can also be seen in the spectrum of serum lipids as the drug lowers the levels of total cholesterol and triacylglycerols. Compared with the results obtained from a group receiving diet without Ca-antagonist premedication, high doses do not reduce the extent of atheromatous plaques.
- MeSH
- aorta thoracica patologie MeSH
- arterioskleróza patologie MeSH
- beta-galaktosidasa krev MeSH
- cholesterol dietní aplikace a dávkování MeSH
- cholesterol krev MeSH
- dipeptidylpeptidasy a tripeptidylpeptidasy krev MeSH
- esterasy krev MeSH
- glukosa-6-fosfátdehydrogenasa krev MeSH
- králíci MeSH
- krevní tlak fyziologie MeSH
- kyselá fosfatasa krev MeSH
- svaly hladké cévní patologie MeSH
- triglyceridy krev MeSH
- verapamil farmakologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-galaktosidasa MeSH
- cholesterol dietní MeSH
- cholesterol MeSH
- dipeptidylpeptidasy a tripeptidylpeptidasy MeSH
- esterasy MeSH
- glukosa-6-fosfátdehydrogenasa MeSH
- kyselá fosfatasa MeSH
- triglyceridy MeSH
- verapamil MeSH
The objective of the work was to follow up on a model of experimental atherosclerosis induced in rabbits by a 1% cholesterol diet the mutual relationship of the deposition of total cholesterol as well as esterified and free fatty acids in the liver and the formation of lipid plaques in the rabbit aorta. The authors investigated also the influence exerted on this process by the s.c. administration of calcium antagonists--Verapamil 0.25 mg.kg-1.day-1 (Lek Ljubl., Jugoslavia), Dilthiazem 2 mg.kg-1.day-1 (Lachema CSFR) and Isradipine 2.5 mg.kg-1.day-1 (Isradipine--N Sandoz, Ltd, Switzerland). The interference of calcium antagonists with the lipid metabolism in the liver as well as the transport mechanism of lipids in the blood stream is differentiated. Verapamil administered in therapeutic doses promotes HDL-cholesterol formation and thus hastens the cholesterol transport from the blood stream into the liver where the latter cumulates. This may be one of the mechanisms of the antiatherogenic action of verapamil. On the other hand, isradipine and in particular dilthiazem administered in treble doses, as compared with therapeutic doses, slightly potentiated the formation of lipid plaques in the rabbit aorta and reduced the HDL-cholesterol level and thus also the cholesterol shift to the liver.
- MeSH
- aorta patologie MeSH
- arterioskleróza metabolismus patologie MeSH
- blokátory kalciových kanálů farmakologie MeSH
- játra metabolismus MeSH
- králíci MeSH
- metabolismus lipidů * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- blokátory kalciových kanálů MeSH
- MeSH
- isoprenalin toxicita MeSH
- králíci MeSH
- mastné kyseliny metabolismus MeSH
- myokard metabolismus patologie MeSH
- nekróza MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- isoprenalin MeSH
- mastné kyseliny MeSH
- MeSH
- beta blokátory farmakologie MeSH
- isoprenalin antagonisté a inhibitory MeSH
- králíci MeSH
- lipolýza účinky léků MeSH
- lokální anestezie MeSH
- morčata MeSH
- propanolaminy farmakologie toxicita MeSH
- srdeční frekvence účinky léků MeSH
- techniky in vitro MeSH
- trachea účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- morčata MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- beta blokátory MeSH
- isoprenalin MeSH
- propanolaminy MeSH
- MeSH
- draslík aplikace a dávkování MeSH
- hořčík aplikace a dávkování MeSH
- isoprenalin aplikace a dávkování MeSH
- izoenzymy MeSH
- králíci MeSH
- kyselina asparagová aplikace a dávkování MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- myokard enzymologie MeSH
- nemoci srdce enzymologie MeSH
- parenterální infuze MeSH
- spektrofotometrie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- draslík MeSH
- hořčík MeSH
- isoprenalin MeSH
- izoenzymy MeSH
- kyselina asparagová MeSH
- L-laktátdehydrogenasa MeSH
