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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The model of atherosclerosis was elaborated by administration of cholesterol to rabbits in daily doses of 70 g per animal over a period of 3 months. The model served to study the effect of the calcium entry blocker Verapamil as to its potential capacity of affecting the extent of atherosclerotic changes. The thoracic aorta, the abdominal aorta, the right coronary artery and the apex of the myocardium were removed for histological evaluation. Atherosclerotic changes were assessed by light microscopy using the method of quantifying the thickening of the intima of vessels. The extent of atherosclerotic changes in the coronary arteries and arterioles was evaluated morphometrically. Further the presence and extent of necroses of the myocardium as well as endothelial proliferation in the capillaries of the cardiac muscle were recorded. Evaluation of the obtained results calculated as percentage of the presence of findings demonstrated a significant protective effect of Verapamil on the parameters studied.
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PMID:[The effect of verapamil on experimental atherosclerosis in rabbits]. 220 21

Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are "pressure-related," such as stroke. However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy. This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties. Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action. Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease. Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies. In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies. Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study. Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease.
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PMID:Anti-atherosclerotic and vasculoprotective actions of calcium antagonists. 225 66

Development of atherosclerotic lesions in animals, preferrably induced by a high-cholesterol diet, can be successfully suppressed by calcium channel blockers such as verapamil, nifedipine, nicardipine and diltiazem. The issue of a beneficial effect of calcium channel blockers on human coronary atherosclerosis is however not yet settled. At present, three prospective randomized clinical trials with calcium channel blockers (Nifedipine, Verapamil, Nicardipine) are being conducted (INTACT, FIPS, Study of the Montreal Heart Institute). Target variable for assessment of progression in these studies is the severity of coronary atherosclerosis evaluated by angiography both at entry into the study and after 2-3 years of treatment. A total of 445 patients after coronary bypass surgery (CABG) were entered in FIPS (Frankfurt Isoptin Progression Study) and randomly allocated to either verapamil 120 mg t.i.d. or placebo. The extent of coronary atherosclerosis is assessed by repeat angiography both 1 year and 3 years after randomization. Three vessel regions are evaluated separately. 1. Native vessels without bypass grafts and segments distal to the peripheral graft anastomosis ("core region") 2. Segments bridged by bypass grafts and 3. Bypass grafts. The 1-year follow-up was completed by 162 patients (Group A = 80 patients; Group B = 82 patients). There was a homogeneous distribution in the two groups for all clinical variables, graft patency rates, and the incidence of clinical events (myocardial infarction, need for cardiac surgery or PTCA, cardiac death). The overall progression rate of atherosclerosis in the first year was expectedly low.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retardation of development and progression of coronary atherosclerosis: a new indication for calcium antagonists? 226 41

Finoptin and sensit produced a favourable effect in the treatment of 290 patients with initial manifestations of deficient blood supply to the brain, encephalopathy attended by circulatory disturbances and ischemic brain insult. Changes in the systemic and cerebral hemodynamics were more pronounced in middle-aged and elderly patients suffering from hypertension or its combination with atherosclerosis.
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PMID:[Calcium antagonists (finoptin and senzit) in the treatment of cerebrovascular disorders]. 258 41

Experimental atherosclerosis in animals preferentially induced by cholesterol-rich food can be successfully suppressed by calcium channel blocking agents such as verapamil, nifedipin, nicardipin, and diltiazem. The question whether calcium channel blockers can favorably influence atherosclerosis in humans remains a matter of debate. A few observational investigations in the past showed positive results of calcium channel blocker therapy in patients with angiographically proven coronary artery disease (CAD). At present three prospective randomized clinical trials are under way (INTACT-study, FIPS-study, study from the Montreal Heart Institute). Target variable is the severity of coronary atherosclerosis assessed by angiography both at entry into the study and after 2-3 years of treatment. 445 patients after coronary bypass surgery were included in the FIPS study (Frankfurt Isoptin Progression Study) and were randomly allocated to either verapamil 120 mg t.i.d. or placebo treatment. Extent of coronary atherosclerosis, assessed by repeat angiography 1 and 3 years after randomization, is expressed by scores with separate evaluation of non-bypassed vessels, segments distal to the peripheral bypass insertion, bypassed segments and grafts. The 1-year follow-up was completed for 162 patients (Group A = 80 patients; group B = 82 patients). There was a homogeneous distribution in both groups for all clinical variables, graft patency rates (76%/75%), and the incidence of clinical events (myocardial infarct, need for cardiac surgery or PTCA, cardiac death: 5%). The overall progression of atherosclerosis in the first year after bypass surgery was small. Thus, the question of whether calcium channel blockers can retard progression of coronary atherosclerosis cannot be answered before completion of the aforementioned trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Can the progression of coronary heart disease be modified by calcium antagonists?]. 269 62

The present study was designed to evaluate the effects of oral verapamil and normal diet on regression of atherosclerotic plaque in cholesterol fed rabbits. Forty-three rabbits were separated into 6 groups and studied for 24 weeks. All groups had a cholesterol diet for the first 12 weeks. Group I was then sacrificed and had 38 +/- 23% (mean +/- standard deviation) aortic plaque. During weeks 13 to 24, group II (cholesterol diet) and group III (normal diet) had similar percentages of aortic plaque: 80 +/- 7% and 78 +/- 22%, respectively. Group IV (cholesterol diet), was treated with oral verapamil for 24 weeks and had significantly less plaque (54 +/- 10%) than group II, (80 +/- 7%). In group V (cholesterol diet), treatment with oral verapamil during weeks 13 to 24 did not significantly reduce plaque (70 +/- 23%), compared to group II, (80 +/- 7%). In group VI, normal diet and verapamil during weeks 13 to 24 significantly reduced aortic plaque (46 +/- 25) when compared to group II (80 +/- 7%). Group VI (46%) did not differ from group I (38%). It is concluded that verapamil combined with a normalized diet can halt the progression of aortic atherosclerosis after a 12 week atherogenic diet in rabbits. Verapamil or diet alone was ineffective in the second 12 weeks. Overall, verapamil was effective in preventing atherosclerosis but was ineffective in causing regression of atherosclerosis.
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PMID:Verapamil and diet halt progression of atherosclerosis in cholesterol fed rabbits. 315 10

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

The effects of calcium entry blockers on stimulated cholesteryl [3H]-oleate deposition in cultured macrophages were characterized in order to elucidate mechanisms underlying possible antiatherosclerotic effects. Stimulation of intracellular cholesteryl [3H]-oleate deposition was initiated by incubation of macrophages with beta-very low density lipoproteins (beta-VLDL). Nifedipine (Class I) markedly reduced cholesteryl [3H]-oleate deposition at all concentrations tested. However, Bay K 8644, a dihydropyridine which is known to stimulate calcium entry, also reduced cholesteryl [3H]-oleate deposition with a similar potency to nifedipine. The effects of three Class II calcium entry blockers were evaluated: verapamil, methoxyverapamil, and diltiazem. Verapamil inhibited cholesteryl [3H]-oleate deposition in a concentration-dependent manner. Similarly, methoxyverapamil reduced cholesteryl [3H]-oleate deposition in a concentration-dependent manner although the reduction was not as great as that produced by verapamil. In contrast, diltiazem at any concentration tested did not inhibit cholesteryl [3H]-oleate deposition. Flunarizine (a Class III calcium entry blocker) produced a modest stimulation of cholesteryl [3H]-oleate deposition at the lowest concentration used (10(-7)M) but marked depression at the highest concentration (10(-5)M). The results indicate calcium entry blockers may exert protective effects on the development of atherosclerosis in animal models of diet-induced hyperlipidaemia by inhibiting intracellular cholesteryl ester deposition, but this effect may not be related to their calcium entry-blocking effects.
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PMID:Inhibition of cholesteryl ester deposition in macrophages by calcium entry blockers: an effect dissociable from calcium entry blockade. 359 69

Bovine aortic endothelial and smooth muscle cells (SMC) and human skin fibroblasts (HSF) were used to study the effect of verapamil on cellular interactions with human low density lipoprotein (LDL). Verapamil, 10 to 50 microM, increased 125I-LDL uptake and degradation by 70% to 200% in the various cells after 24 to 48 hours of incubation. The increase in the total amount of LDL endocytosed, labeled with 3H-cholesteryl linoleate (3H-CL), was comparable to that determined with 125I-LDL. In HSF and SMC, a delay in 125I-LDL degradation and hydrolysis of 3H-CL was seen in cells treated for 3 to 24 hours with verapamil. Pretreatment of HSF with 50 microM verapamil for 24 hours and incubation with 2 to 50 micrograms 125I-LDL protein/ml for 1 hour resulted in a 50% to 200% increase in heparin releasable and in a 40% to 130% increase in cellular 125I-LDL. Thus, the increase in 125I-LDL binding and uptake in verapamil-treated cells was apparently due to an increase in receptor number, rather than in receptor affinity. The effect of verapamil on LDL uptake and degradation was also seen in cells that were pretreated for 24 hours and incubated with 125I-LDL in the absence of verapamil. The effect of verapamil was not apparent in LDL receptor-negative cells. Cycloheximide blocked the verapamil effect. The Na+ channel blocker, tetrodotoxin x 10(-6) M, caused a 30% to 50% increase in the total amount of LDL endocytosed, but no delay in LDL degradation; amiloride 2 x 10(-3) M was not effective. If the presently described effect of verapamil also occurs in vivo, this might contribute to the reported beneficial effects of Ca++ channel blockers in experimental atherosclerosis by promoting transfer of LDL cholesteryl ester from the aortic interstitium to a catabolic compartment.
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PMID:Verapamil enhances receptor-mediated endocytosis of low density lipoproteins by aortic cells in culture. 396 7

Verapamil and other slow channel calcium antagonists have been reported to retard atherosclerosis in rabbits fed a high cholesterol diet. Because atherosclerosis in such a model may differ significantly from human atherosclerosis, experiments were conducted to prevent atherosclerosis with verapamil in the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is a genetic, metabolic and pathologic model of homozygous familial hypercholesterolemia. At 2 months of age, 23 WHHL rabbits were divided into two groups since earlier studies showed no macroscopic atherosclerosis at 2 months. Group A (n = 11) was fed standard rabbit chow for 6 months. Group B (n = 12) received oral verapamil (46 mg/kg per day) absorbed in the identical chow as fed to Group A and subcutaneous verapamil (0.25 mg/kg twice daily 6 days a week). In Group B, mean serum verapamil concentrations (+/- SEM) averaged 16.9 +/- 1.9 ng/ml at 3 hours after subcutaneous injection. Sex ratios and serum cholesterol concentrations were the same in both groups. The percent of aortic surface area with visible plaque in Group A versus B was 49 +/- 7 versus 43 +/- 7%, respectively, of the entire aorta, and 61 +/- 5 versus 65 +/- 5%, respectively, of the proximal 3 cm of aorta (p = NS). Thus, verapamil did not suppress atherosclerosis in WHHL rabbits at serum drug levels greater than those reported to be effective in other models.
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PMID:Failure of a slow channel calcium antagonist, verapamil, to retard atherosclerosis in the Watanabe heritable hyperlipidemic rabbit: an animal model of familial hypercholesterolemia. 400 71


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