ABSTRACT
The beta- and alpha-adrenoceptor blocking activity, the specificity of its beta-adrenoceptor blocking action, partial agonistic and membrane-stabilizing properties, as well as antihypertensive, antiarrhythmic, and anti-ischemic effects were studied. Proxodolol was shown to be superior to labetalol in its beta-adrenoceptor blocking action and similar to it in its alpha-adrenoceptor blocking agent. The drug has no a partial agonistic activity and produces a moderate membrane-stabilizing action. Proxodolol proved to be effective in treating experimental hypertension and arrhythmias. It exhibits anti-ischemic activity.
Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Oxadiazoles/pharmacology , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Animals , Arrhythmias, Cardiac/drug therapy , Cats , Cell Membrane/drug effects , Dogs , Drug Evaluation, Preclinical , Heart/drug effects , Heart Rate/drug effects , Hypertension/drug therapy , In Vitro Techniques , Labetalol/pharmacology , Male , Oxadiazoles/therapeutic use , Oxprenolol/pharmacology , Propranolol/pharmacology , Rabbits , RatsABSTRACT
The effects of phenothiazine drugs on the levels of cholesterol in smooth cells of the human aortic intima. Two antiarrhythmics (ethacizin and ethmozine) and two neuroleptics (trifluoperazine and chlorpromazine) were evaluated. The three agents ethacizin, trifluoperazine, and chlorpromazine given in concentrations of 10(-7) to 10(-5) M were ascertained to cause intracellular cholesterol accumulation, whereas ethmozine produced no effects on the intracellular levels of cholesterol. Ethacizin failed to cause cholesterol accumulation when the cells were incubated with ethacizin in the culture medium supplemented with lipid-deficient serum. Ethacizin in a concentration o 10(-5) M was shown to inhibit the synthesis of cholesterol esters and had no action on the intracellular synthesis of steroids.
Subject(s)
Aorta/drug effects , Arteriosclerosis/chemically induced , Phenothiazines/adverse effects , Anti-Arrhythmia Agents/adverse effects , Aorta/chemistry , Cells, Cultured , Chlorpromazine/adverse effects , Cholesterol/analysis , Culture Media , Humans , Moricizine/adverse effects , Moricizine/analogs & derivatives , Psychotropic Drugs/adverse effects , Trifluoperazine/adverse effectsABSTRACT
The action of two antiarrhytmic drugs, moracizine (MOR, CAS 31883-05-3) and ethacizine (ETHA, CAS 33414-33-4) on receptors of potential-operated CA-channels has been investigated. ETHA binding to verapamil receptors was more effective than that of MOR (IC50 = 0.53 +/- 0.08 mumol/l, respectively). The Hill coefficient for ETHA binding was similar to that of verapamil (0.64 +/- 0.09 and 0.60 +/- 0.10, respectively). Interaction of ETHA and MOR with dihydropyridine receptors in concentrations up to 10 mumol/l was similar that of verapamil, however, MOR was less potent. MOR and ETHA did not interact with calmodulin and troponin C at concentrations up to 100 mumol/l. The influence of MOR and ETHA on enzymes dependent on Ca-binding proteins (phosphodiesterase and actomyosin ATPase) was not observed up to 100 mumol/l. Comparison of clinical and electrophysiological data with these results allows the conclusion that ETHA exerts Ca-blocking effects by the interaction with verapamil receptors on potential-operated Ca-channels.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Calcium-Binding Proteins/metabolism , Moricizine/pharmacology , Phenothiazines/pharmacology , Receptors, Nicotinic/drug effects , Adenosine Triphosphatases/metabolism , Animals , Calcium Channels , Chlorpromazine/pharmacology , Electrophysiology , In Vitro Techniques , Ligands , Membrane Potentials/drug effects , Phosphoric Diester Hydrolases/metabolism , Protein Binding , Rabbits , Verapamil/pharmacologyABSTRACT
Content of tocopherol and total antiradical activity of hydrophobic antioxidants were estimated in human blood platelets. Two hydrophobic antioxidants--tocopherol and ubiquinone were detected in hexane extracts of thrombocytes using thin-layer chromatography. After incubation of thrombocytes with N-ethyl maleimide content of malonyl dialdehyde was increased and of tocopherol--decreased, receptor-dependent increase of Ca2+ concentration in cytoplasm was potentiated, while the Ca(2+)-blocking effect of nitroglycerol was decreased. Nitroglycerol did not inhibit the N-ethyl maleimide effect on content of malonyl dialdehyde in blood platelets. Addition of exogenous vitamin E to thrombocytes did not affect the receptor-dependent increase of Ca2+ concentration. Ascorbic acid inhibited the receptor-dependent increase of Ca2+ concentration. The data obtained suggest that nitrates may be used more rationally in combination with antioxidants and/or inhibitors of cyclooxygenase.
Subject(s)
Antioxidants/pharmacology , Blood Platelets/metabolism , Calcium/blood , Lipid Peroxidation/drug effects , Ascorbic Acid/pharmacology , Blood Platelets/drug effects , Cell Membrane/drug effects , Cell Membrane/metabolism , Chromatography, Thin Layer , Ethylmaleimide/pharmacology , Humans , Malondialdehyde/metabolism , Nitroglycerin/pharmacology , Ubiquinone/metabolism , Vitamin E/metabolism , Vitamin E/pharmacologyABSTRACT
There is a possibility that the cardioprotective effect of adaptation to intermittent hypoxia is due to changes in receptors apparatus of the heart. In this connection the effect of preliminary adaptation to intermittent hypoxia (4 hours per day at the altitude of 4000 m during 40 days) on the state of beta-receptors-adenylate-cyclase system and same other receptors of the heart were studied. It was shown that at the end of the course of adaptation the number of beta-adrenoceptors in the heart was increased with simultaneous decrease in basal adenylate-cyclase activity, accompanied by the diminution of its response to beta-agonist. The number of beta-adrenoceptors was increased by 48% and their affinity to ligand was increased by almost 2 times. The revealed decrease in the reactivity of beta-receptor-adenylate-cyclase system and increase of alpha 1-adrenoreactivity can play a certain role in the mechanism of cardioprotective effect of adaptation to hypoxia.
Subject(s)
Adaptation, Physiological , Heart/physiopathology , Hypoxia/physiopathology , Receptors, Adrenergic, alpha/physiology , Adenylyl Cyclases/analysis , Animals , Heart/innervation , Periodicity , Rats , Time FactorsABSTRACT
Results of the experiments evidence that a combination of three factors, limiting the Ca2+ concentration increase in myocardial cell, can play a role in the cardioprotective effect of adaptation of rats to short-term immobilization stress (every second day for a month) are presented. Those factors are as follows: desensitization of alpha 1-adrenoreceptors, M-cholinoreceptors up-regulation and reduced number of voltage-dependent Ca2+ channels in the myocardial membranes.
Subject(s)
Calcium Channels/metabolism , Calcium/metabolism , Models, Psychological , Myocardium/metabolism , Receptors, Adrenergic, alpha/metabolism , Stress, Psychological/metabolism , Adaptation, Physiological/physiology , Adaptation, Psychological/physiology , Animals , Male , Rats , Restraint, Physical , Time FactorsABSTRACT
The beta-adrenoblockers anapriline and visken and the calcium antagonist corinfar were studied for effects on the atherogenic properties of the sera from patients with coronary heart disease who took the drugs. The study was performed by using cultured atherosclerotically altered human aortic smooth muscle cells. A single dose of anapriline, 80 mg, and that of visken, 20 mg, were found to give rise to or to enhance atherogenic properties of the patients' sera, while that of corinfar, 20 mg, yielded their antiatherosclerotic properties.
Subject(s)
Coronary Disease/blood , Nifedipine/pharmacology , Pindolol/pharmacology , Propranolol/pharmacology , Adult , Cells, Cultured , Coronary Disease/drug therapy , Humans , Male , Middle Aged , Muscle, Smooth, Vascular , Nifedipine/therapeutic use , Pindolol/therapeutic use , Propranolol/therapeutic useABSTRACT
Cordarone was studied for effects on the pharmacological receptors of myocardial potential-dependent Ca channels, on the receptor-dependent increase in platelet Ca2+ content, on muscarinic cholinergic receptors of the M1- and M2-type, and on calmodulin regulation of cAMP phosphodiesterase (PDE). Without showing selectivity, cordarone is able to interact both with M1-, and M2-muscarinic choline receptors with Ki = 5.3-5.6 microM. Cordarone was found to displace [3H]-nitrendipine with Ki = 1.25 microM and [3H]-desmethoxyverapamil with Ki = 1 microM. The pattern of ligand displacement suggests that the interaction of cordarone with these receptors has no competition. Cordarone was demonstrated to affect neither PDE activity nor its activation with calmodulin. Cordarone suppressed a platelet activation factor-induced increase in intracellular Ca2+ levels in the thrombocytes. Thus, cordarone is capable of affecting Ca2(+)-dependent processes at Ca2+ entry across the potential-dependent Ca channels and influencing the receptor-dependent platelet Ca2+ mobilization and muscarinic cholinergic regulation. The above effects may underlie antiarrhythmic action and determine vascular dilating and anti-fibrillating properties of cordarone.
Subject(s)
Amiodarone/pharmacology , Calcium/metabolism , Calmodulin/metabolism , Heart/drug effects , 3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Animals , Blood Platelets/metabolism , Calcium Channels/metabolism , Heart/physiology , Humans , In Vitro Techniques , Myocardium/metabolism , Rabbits , Receptors, Cholinergic/metabolism , Receptors, Muscarinic/metabolismABSTRACT
The data bearing witness to realization of the cytostatic activity of alkylating agents by means of interaction with cell membrane receptors was obtained. Alkylating agents block receptors of the polyphosphoinositol system. It is shown that chloralkylamines inhibiting sites coincide with M-++cholinomimetics and alpha-adrenergic receptors, inhibitors of H-histamine receptors, cyclo- and lypoxigenase inhibitors. Such likeness is determined by identical structures of the molecule active part, and quantum-chemical calculations.
Subject(s)
Alkylating Agents/pharmacology , Antineoplastic Agents/pharmacology , Cell Membrane/drug effects , Animals , Binding Sites , Cerebral Cortex/ultrastructure , Corpus Striatum/ultrastructure , In Vitro Techniques , Liver/ultrastructure , Models, Molecular , Myocardium/ultrastructure , RabbitsABSTRACT
The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied. Both the blockers and activators of slow potential-dependent Ca2+ channels induced a un-competitive inhibition of the CM-dependent PDE activity. 1.4-DHP was found to replace the fluorescent probe, diS-C3-(5), from the Ca2(+)-dependent calmodulin-dye complex (K0.5 = 4-60 microM) but at concentrations below 100 microM had no effect on the Ca2(+)-dependent troponin C-dye complex. Darodipine (100 microM) did not interact with the proteins. The 1.4-DHP interaction with CM did not interfere with PDE activation. It is concluded that 1.4-DHP may affect Ca2+ dependent processes not only at the levels of activation or blocking of Ca2+ channels, but also through regulation of Ca2(+)-CM dependent enzymes.
Subject(s)
2',3'-Cyclic-Nucleotide Phosphodiesterases/metabolism , Calcium Channel Agonists/pharmacology , Calcium Channel Blockers/pharmacology , Calcium-Binding Proteins/metabolism , 2',3'-Cyclic-Nucleotide Phosphodiesterases/antagonists & inhibitors , Animals , Binding, Competitive , Calcium Channel Agonists/metabolism , Calcium Channel Blockers/metabolism , Calmodulin/metabolism , Cattle , Enzyme Activation , In Vitro Techniques , Kinetics , Rabbits , Troponin/metabolismABSTRACT
To investigate the effects of calcium antagonists on atherosclerotic cellular indices, [3H]thymidine incorporation and intracellular cholesterol content, primary culture of cells isolated from subendothelial intima of human atherosclerotic aorta was used. Among tested drugs were: verapamil, nifedipine, diltiazem, papaverin, nicardipine, D-600, cinnarizine, PN 200 110 and PY 108 068. Verapamil proved to be the most effective. It significantly reduced the total intracellular cholesterol and sharply decreased the incorporation of [3H]thymidine. With respective efficacy verapamil was followed by nifedipine and PY 108 068. Neither beta-blocker (metoprolol) nor nitrate (nitroglycerin) modified antiatherosclerotic effects of calcium antagonist (nifedipine). Calcium agonist Bay K 8644 which facilitates the penetration of calcium into cells caused the accumulation of intracellular cholesterol and stimulated cell proliferation. Simultaneous addition of nifedipine and Bay 8644 led to the inhibition of the agonist's atherogenic effect. Thus, facilitation of calcium influx into cells causes atherosclerotic alterations in the arterial cells; atherogenic calcium effects are inhibited by calcium channel blockers. Furthermore, based on the results of application of blood plasma from patients treated with calcium antagonists or beta-blocker to primary cultures of atherosclerotic cells, it can be assumed that calcium antagonists affect an anti-atherosclerotic and beta-blockers an atherogenic action.
Subject(s)
Arteriosclerosis/pathology , Calcium Channel Blockers/pharmacology , Endothelium, Vascular/drug effects , Muscle, Smooth, Vascular/drug effects , Adrenergic beta-Antagonists/pharmacology , Aorta/drug effects , Aorta/pathology , Cell Division/drug effects , Cholesterol/metabolism , Culture Techniques , DNA Replication/drug effects , Endothelium, Vascular/pathology , Humans , Muscle, Smooth, Vascular/pathology , Nitrates/pharmacologyABSTRACT
Synaptosomes and synaptic membranes were studied in brain cortex of rats after 6 hrs emotional-painful stress. No alterations were observed in beta-adrenoreceptors, adenylate and guanylate cyclases to the end of the second day after the acute stress action.
Subject(s)
Adenylyl Cyclases/metabolism , Cerebral Cortex/enzymology , Stress, Psychological/enzymology , Synaptosomes/enzymology , Acute Disease , Animals , Binding, Competitive , Dihydroalprenolol , Guanylate Cyclase/metabolism , Rats , Rats, Inbred Strains , Receptors, Adrenergic, beta/metabolismABSTRACT
Nitroglycerin, isosorbide dinitrate and sodium nitroprusside, like nifedipine, were found to inhibit the receptor-provoked increase of cytosolic free calcium concentration in human platelets loaded with 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N',N' - tetraacetate. Sodium nitroprusside and nitroglycerin induced elevation of cyclic guanosine 3',5'-monophosphate content in platelets which correlated with their calcium-blocking activity. Methylene blue and epinephrine decreased the calcium-blocking effect and the influence of nitroglycerin on cyclic guanosine 3'-5'-monophosphate content, but failed to suppress the inhibitory effect of sodium nitroprusside. Ascorbic acid increased the calcium blocking effect of sodium nitroprusside and its influence on cyclic guanosine 3'-5'-monophosphate content, but did not alter the inhibitory effect of nitroglycerin. In order to evaluate the relationship between the mode of action of nitrates at cellular level and their vasodilatory effectiveness, we studied the circulatory response of the forearm to isosorbide dinitrate and the influence of nitroglycerin on free calcium concentration in the platelets in 10 patients with chronic heart failure. We established a significant positive correlation between the basal values for venous tone and its peak decrease after administration of the 10-mg dose of isosorbide dinitrate. A correlation was also found between the deviation of maximal decrease of venous tone by this dose of isosorbide dinitrate from the regression line (the relationship between the basal venous tone and its lowering by the drug) and mean inhibitory concentration values for nitroglycerin in blocking that proportion of the rise of calcium ion concentration in platelets due to blocking of the platelet-activating factor. Thus, nitrates, like calcium antagonists, inhibit the receptor-provoked calcium supply to the contractile system of the cells so neutralizing the effects of increased concentrations of vasoconstrictors. This suggests that the effectiveness of nitrates appears to be positively related to the contribution of receptor-induced increase of cytosolic free calcium concentration in vasoconstriction together with their capacity to raise cyclic guanosine 3',5'-monophosphate.
Subject(s)
Blood Platelets/drug effects , Calcium/metabolism , Heart Failure/drug therapy , Nitrates/therapeutic use , Adult , Humans , Isosorbide Dinitrate/pharmacology , Middle Aged , Nifedipine/pharmacology , Nitroglycerin/pharmacology , Nitroprusside/pharmacology , PlethysmographyABSTRACT
Cordarone was examined for its effects on alpha- and beta-adrenergic receptors and adenylate cyclase (AC) of some tissues. Cordarone was shown to suppress the binding of [3H]-clonidine with alpha 2-receptors of the rabbit brain (Ki = 4 microM) and that of [3H]-prazosin with alpha 1-receptors of the rat liver (Ki = 22 microK), but not to displace [3H]-dihydroalprenolol from rabbit cardiac and pulmonary beta 1-receptors and from beta 2-receptors of rat reticulocytes and human lungs. Cordarone failed to affect the activity of rabbit heart and lung AC, as well as that of thrombocytes and human lungs, but showed a 80% inhibition of the activating effect of isoproterenol on reticulocyte AC. It was suggested that the effect of cordarone on reticulocytes was not mediated by beta-receptors and was tissue specific and dependent on the characteristics of AC regulation in these cells. Cordarone's antiadrenergic effect found in vitro may be one of the causes of its coronary dilating and antiarrhythmic effects.
Subject(s)
Amiodarone/pharmacology , Receptors, Adrenergic, alpha/drug effects , Receptors, Adrenergic, beta/drug effects , Viscera/drug effects , Adenylyl Cyclase Inhibitors , Adenylyl Cyclases/metabolism , Animals , Blood Cells/drug effects , Blood Cells/physiology , Brain/cytology , Brain/drug effects , Brain/enzymology , Depression, Chemical , Heart/drug effects , Humans , In Vitro Techniques , Lung/cytology , Lung/drug effects , Lung/enzymology , Myocardium/cytology , Myocardium/enzymology , Rabbits , Rats , Receptors, Adrenergic, alpha/physiology , Receptors, Adrenergic, beta/physiology , Viscera/cytology , Viscera/enzymologyABSTRACT
Interaction of the antiarrhythmics moracizine (moricizine, ethmozine, ETHM) and ethacizine (ETHA), the ethyl ester hydrochlorides of 10-(3-R-propionyl)-phenothiazine-2-carbamic acid (where R is morpholine or diethylamine, respectively), with muscarinic cholinergic alpha- and beta-adrenergic systems and histamine H1 receptors (H1-R) has been studied. ETHA and ETHM displaced [3H]-quinuclidinyl benzilate ([3H]-QNB) from muscarinic receptors of M2 type (M2-R) of rabbit heart with Ki = 0.65 +/- 0.07 and 21 +/- 1 mumol/l in atria, 0.77 +/- 0.06 and 22 +/- 3 mumol/l in ventricles; [3H]-pirenzepine ([3H]-PZ) from M1-R of rabbit brain cortex with Ki = 0.70 +/- 0.04 and 3.1 +/- 0.1 mumol/l, respectively. However, only ETHA inhibited the effect of carbachol on rabbit heart adenylate cyclase (AC). ETHM and ETHA bound to alpha 1- and alpha 2-adrenergic receptors (AR) and H1-R of rabbit brain cortex with an affinity in the range of 7-50 mumol/l. Both drugs did not influence epinephrine-sensitive AC of human platelets in concentrations up to 100 mumol/l. They neither bound to beta 1-AR of rabbit heart and beta 2-AR of rat reticulocytes, nor influenced the regulation of AC by isoprenaline (isoproterenol) in the same membrane preparations in concentrations up to 100 mumol/l. The present data shows that ETHA and ETHM in therapeutic doses may have M-cholinolytic properties, ETHA being more potent than ETHM. Coupled with the results of other investigators it might explain the wider spectrum of clinical effects of ETHA as compared with ETHM.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Phenothiazines/pharmacology , Receptors, Drug/drug effects , Animals , Atropine/pharmacology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Heart/drug effects , In Vitro Techniques , Moricizine , Myocardium/metabolism , Rabbits , Rats , Reticulocytes/drug effects , Reticulocytes/metabolismABSTRACT
In cultured human cells, beta-adrenoblockers such as propranolol, alprenolol, metoprolol, atenolol, pindolol, and thymolol, as well as sera from patients with coronary heart disease were examined for atherogenic activity following a single administration of propranolol (80 mg) and pindolol (10 mg). Addition of the beta-adrenoblockers to the cell culture was demonstrated to enhance cellular total cholesterol levels and to stimulation their proliferation. Propranolol and pindolol given in a single dose was found to result in the appearance of atherogenic properties of the patients' sera.
Subject(s)
Adrenergic beta-Antagonists/adverse effects , Aorta/metabolism , Aortic Diseases/chemically induced , Arteriosclerosis/chemically induced , Cholesterol/metabolism , Endothelium, Vascular/metabolism , Aorta/drug effects , Aorta/pathology , Culture Media , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Humans , In Vitro Techniques , Stimulation, ChemicalABSTRACT
Epinephrine (E) and norepinephrine (NE) alone did not increase free intracellular Ca2+ ([Ca2+]i) in human platelets loaded with Quin-2 or Fura-2; however, they did potentiate the effects of vasopressin (VP), serotonin (S) and platelet activating factor (PAF). The synergism in [Ca2+]i increase was also obtained in the presence of VP together with PAF, S with PAF as well as VP with S. The effect of E or NE was blocked by yohimbine and phentolamine. Prazosin was less effective, while propranolol had no effect at all. Clonidine did not potentiate the effects of VP, S or PAF on [Ca2+]i; however, it did block the potentiation induced by E or NE. E potentiated the VP-induced 45Ca2+ uptake as well as VP-stimulated inositol 1,4,5-trisphosphate (IP3) formation. E alone did not change significantly the level of IP3 in platelets, nor did it influence the cyclic AMP level. The experimental results suggest that both Ca2+ influx and polyphosphoinositide breakdown underlie the mechanism of potentiation.
Subject(s)
Blood Platelets/metabolism , Calcium/blood , Receptors, Adrenergic, alpha/metabolism , Cyclic AMP/metabolism , Depression, Chemical , Epinephrine/metabolism , Humans , Norepinephrine/metabolism , Phentolamine/pharmacology , Platelet Activating Factor/metabolism , Prazosin/pharmacology , Propranolol/pharmacology , Serotonin/metabolism , Stimulation, Chemical , Vasopressins/metabolism , Yohimbine/pharmacologyABSTRACT
The effect of phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PK-C) on lipid peroxidation (LPO) in rat liver homogenates and microsomes was studied. PMA (10(-10) to 10(-6) M) produced a concentration-dependent inhibition of LPO, which was greatly decreased by polymyxin B (PxB) (an inhibitor of PK-C). The non-active analogue of PMA, 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) exerted no inhibitory effect. The adenylate cyclase activator, forskolin (FK) (10(-6) M) abolished the inhibitory effect of PMA on LPO. PMA and FK did not inhibit LPO in liposomes. It is suggested that LPO in biomembranes could be regulated by PK-C, whose inhibitory effect might be prevented by cAMP-dependent protein kinases.
Subject(s)
Lipid Peroxidation/drug effects , Liver/metabolism , Microsomes, Liver/metabolism , Animals , Colforsin/pharmacology , Male , Polymyxin B/pharmacology , Rats , Rats, Inbred Strains , Second Messenger Systems , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
We investigated the effects of stable analogues of prostacyclin (carbacyclin) and thromboxane A2 (U46619) and various calcium antagonists on atherosclerotic cellular indices, intracellular cholesterol content and [3H]thymidine incorporation. Primary culture of human subendothelial cells derived from atherosclerotic plaques of aorta was used. Carbacyclin reduced cholesterol accumulation and cell proliferation. U46619 in opposite to carbacyclin stimulated this processes. In general, carbacyclin exerted a direct antiatherosclerotic and U46619 - atherogenic action in culture. Calcium antagonists: dihydropyridines, verapamil derivatives and diltiazem demonstrated antiatherosclerotic properties themselves and potentiated carbacyclin effect but restricted atherogenicity of U46619.