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

Atherosclerosis results from multiple factors, and involves several mechanisms including endothelial monocyte and smooth muscle cell changes, cholesterol accumulation, lumen stenosis, necrosis, mineralization, plaque hemorrhage, rupture, and thromboembolism. Calcium antagonists have been shown in hypercholesterolemic animal models to reduce atherosclerosis. This effect cannot be explained on the basis of changes in blood pressure, therefore suggesting that calcium channel antagonists have a direct effect on arterial wall processes associated with plaque evolution. The antiatherosclerosis properties of calcium antagonists have been tested in human subjects and suggest that these compounds inhibit new lesion development. Recent developments in B-mode ultrasonography allow investigators to detect and monitor atherosclerosis noninvasively. This method is being used in several trials within the U.S. and Europe to evaluate treatment effects on carotid atherosclerosis. Carotid artery disease is associated with transient ischemic attacks, ischemic cerebral infarction, and with risk for coronary artery disease. B-mode ultrasonography is a powerful method for monitoring atherosclerosis progression. The combination of this technology with calcium antagonist treatment will allow evaluation of the efficacy of intervention on the arterial wall during the asymptomatic stages of atherosclerosis evolution.
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PMID:Antiatherogenic properties of calcium antagonists. 172 13

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.
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PMID:[The effect of calcium channel blockers on experimental hypercholesteremia in rabbits. Biochemical and histochemical study]. 178 82

Calcium channel blockers may retard development and progression of coronary arteriosclerosis in man because of protective effects on membranes, (especially the endothelium), relaxation of vessel walls, inhibition of various platelet functions, impairment of proliferation and migration of smooth muscle cells in the vessel wall, and an improvement of vascular cholesterol metabolism. In animal trials development of atheromas in large arteries induced by cholesterol-rich food and other stimuli of atherogenesis could be successfully retarded by a broad variety of calcium channel blockers. Some clinical observations in patients with coronary artery disease pointed at positive effects of calcium antagonists in coronary arteriosclerosis. To date, the results of three prospective placebo-controlled trials with calcium antagonists in coronary arteriosclerosis are available. In all trials progression of atherosclerosis was assessed by serial angiograms: 1) INTACT (nifedipine: 20 mg four times daily; observation period: 3 years, two coronary angiograms); 2) Study of the Montreal Heart Institute (nicardipine: 30 mg three times daily; observation period: 2 years, two coronary angiograms); 3) FIPS (Frankfurt Isoptin Progression Study) (verapamil: 120 mg three times daily; observation period: 3 years, three coronary angiograms). Target variables in these studies were progression or regression of preexisting lesions, development of new lesions and the incidence of vessel occlusions. The INTACT and the Nicardipine studies preferably included patients in early stages of coronary artery disease. The patients of FIPS who were entered into the study immediately after coronary bypass surgery suffered from severe, advanced coronary artery disease. In the latter study progression of coronary artery disease was assessed separately in different vascular regions (bypassed and non-bypassed segments) and in the bypass grafts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Modification of coronary arteriosclerosis in man by calcium antagonists?]. 179 51

The pathogenesis of atherosclerosis has been extensively studied and the cellular aspects increasingly characterized. This review will focus on the basic pathology, presumed cellular events, cellular interactions, cell-lipid relationships, and potential therapies of atherosclerosis. Fatty streaks, fibrous plaques, and complicated plaques are the pathologic hallmarks of atherosclerosis. These lesions insidiously progress, and symptoms appear to develop when the plaque luminal surface destabilizes. The major cellular contributors to plaque development are monocytes/macrophages, endothelial cells, smooth muscle cells, and, to a lesser degree, lymphocytes and platelets. They interact in a complicated fashion. Growth factors and cytokines produced by these cells are also of great importance for cell-cell interaction. Hemodynamic factors contribute to atherogenesis at preferential sites within the arterial vasculature, presumably by effects on the cellular mechanisms. Hyperlipidemia, especially elevations of total and LDL-cholesterol, has been well characterized as an atherosclerotic risk factor. Cellular modification of LDL-cholesterol, primarily by oxidation, leads to more rapid uptake by macrophage-derived foam cells, enhancing plaque growth by this and other mechanisms. These observations may unify the cellular and lipid contributors to atherogenesis. Therapies directed at the cellular contributors to atherosclerosis are being assessed. Dietary n-3 fatty acid supplementation reduces the extent of experimental atherosclerosis, and human studies are in progress. Many potential cellular effects of n-3 fatty acids have been demonstrated. Other potential therapies for atherosclerosis that probably work at the cellular level include calcium channel blockers, antioxidants, and heparinoids. An exciting new era of atherosclerosis research and, hopefully, therapy has dawned, as knowledge about its cellular basis accrues.
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PMID:Atherosclerosis: cellular aspects and potential interventions. 185 95

Available data on results of lipid-acting drug trials investigating the prevention or treatment of atherosclerotic cardiovascular disease have conclusively shown that: (a) The beneficial results may not be specific for a given pharmacological group of drugs (i.e., niacin, resins, fibrates, reductase inhibitors). (b) For lipid-acting drugs, the extent of cardiovascular benefit may be related to the extent of the effect on blood lipids. (c) Some drugs may be acting by affecting factors not necessarily related to blood lipid levels (i.e., calcium channel blockers and antioxidants of low-density lipoproteins. (d) The differences in endpoints begin to appear after the second year of intervention. (e) The effects on atherosclerosis can be measured objectively by modern angiographic techniques. (f) Patient's signs and symptoms of disease can be beneficially modified. (g) The long-term safety record of the tested drugs seems adequate. (h) The risk-benefit ratio justifies long-term drug treatment of dyslipidemias in patients not responding to life-style intervention.
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PMID:Drug intervention trials in dyslipidemia: the past and the future. 204 59

The frequent concurrence of other cardiovascular risk factors in hypertensive patients, such as obesity and diabetes mellitus, suggests that overlapping genetic and environmental factors may contribute to the common metabolic and cardiovascular derangements observed in these populations. Hypertension and hyperglycemia accelerate atherosclerosis in diabetics, and play an important role in associated morbidity and mortality. Several abnormalities in blood pressure regulatory systems such as the renin-angiotensin system, the sympathetic nervous system, and sodium/volume control have been described in diabetes mellitus. Sodium retention and cardiovascular hyperreactivity appear to occur early in the course of diabetes mellitus, even at normal blood pressure levels and before onset of renal failure, and could set the stage for the development of hypertension. The relationship between obesity and hypertension is also well-established, and may reflect metabolic and cardiovascular adaptations in obese subjects which predispose to blood pressure elevations. Obese subjects display changes in sympathetic nervous system activity, sodium metabolism, and vascular hemodynamics. Sodium-sensitive blood pressure responses in the obese may be secondary to increased cardiac output or fluid volume, and are directly related to circulating insulin levels. Certain metabolic and vascular characteristics of obesity and diabetes mellitus are found in patients with essential hypertension. It has been suggested that insulin and insulin resistance may be the common link between these risk factors. Improved understanding of metabolic considerations in the treatment of obese and diabetic hypertensives should lead to more careful selection of medications that avoid metabolic complications. Although diuretics and beta-blockers may be useful in some patients, there are several reasons not to recommend their use as initial therapy in obese and diabetic hypertensives. On the other hand, calcium channel blockers and angiotensin converting enzyme inhibitors are highly effective, with minimal effects on metabolic parameters, and are well-suited as first-line therapy in the treatment of obese and diabetic hypertensives.
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PMID:Metabolic considerations in hypertension. 207 23

Clinical experience and epidemiological observations have demonstrated that some hypertensive patients experience progression of atherosclerotic vascular disease despite successful control of hypertension. Thus, there appears to be a discordance relative to the benefits of antihypertensive therapy--'pressure'-related but not 'atherosclerotic' complications are prevented by BP control with conventional antihypertensive therapy. The effects of antihypertensive drugs on atherosclerotic complications of hypertension is a subject of major clinical importance. The question is whether or not different classes of antihypertensive drugs exert dissimilar vasculoprotective actions independent of their BP lowering effects. There is considerable experimental data to implicate a relationship between calcium and lipoprotein metabolism at the vascular site. The calcium ion may play a role in the steps culminating in the formation of atherosclerotic plaques. Evidence has been presented that calcium channel blockers may modify experimental arterial calcinosis and atherosclerosis. At least a couple of published trials have shown that calcium antagonists indeed prevent/attenuate atherosclerotic lesions in patients with coronary artery disease. These observations underscore the significance of a new dimension in cardiovascular drug therapy--that is the vasculoprotective and antiatherosclerotic effects of calcium antagonists.
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PMID:Antiatherosclerotic and vasculoprotective effects of calcium antagonists: clinical implications. 209 Aug 36

It is well established that renin release from the juxtaglomerular epithelioid cells in the media of the afferent arteriole strongly depends on the mean renal perfusion pressure, whereas a possible influence of the pulsation of blood pressure on renin release has only occasionally been investigated, and the results are contradictory. Such an influence on renin release cannot be excluded because pulsation is known to modulate arterial baroreceptors and vascular tone in some resistance vessels. In the isolated perfused rat kidney, we found a pulsation amplitude-dependent inhibition of renin release that could be blocked either by vasodilatation or by calcium channel blockade. The inhibition occurred at perfusion pressures between 85 and 125 mm Hg. The underlying pulsation pressure-sensitive mechanism has to be ascribed integrating properties, because a constant-flow pressure rise to the "systolic" value of pulsatile perfusion resulted in virtually the same inhibition of renin release. Moreover, a reduced urine flow during pulsatile perfusion provides evidence for preglomerular constriction under these conditions. It is concluded that, besides pathological changes of renal perfusion pressure, variations of the pulse amplitudes, e.g. resulting from renal artery stenosis or atherosclerosis, may also influence renin release and contribute to renovascular hypertension.
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PMID:Influence of pulsatile perfusion upon renin release from the isolated perfused rat kidney. 218 59

Several chemical classes of calcium channel blockers (CCBs) inhibit atherosclerotic lesion formation in rabbit models by reduction of calcium, lipid, and matrix accumulation in the arterial wall. The mechanisms of these antiatherogenic effects are under investigation. Smooth muscle cells and macrophages, which synthesize matrix products and accumulate intracellular lipids, play a central role in lesion formation. Smooth muscle cell hyperplasia, with intracellular and functional changes, is common to both atherosclerosis and hypertension. The antiatherogenic properties of CCBs may be related in part to the protection of arterial cells from calcium overload through inhibition of calcium flux across voltage-regulated ion channels. CCBs may also inhibit cell migration, influence the uptake and catabolism of lipoproteins, alter smooth muscle matrix synthesis, and promote the depletion of intracellular cholesteryl ester stores. It appears that CCBs may inhibit the development of atherosclerotic lesions by two sets of mechanisms: alteration of lipid metabolism in smooth muscle cells and regulation of calcium-initiated or -accelerated intracellular processes.
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PMID:Calcium channel blockers and atherosclerosis. 222 Jul 98

To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions.
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PMID:A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis. 224 48


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