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

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

In 8 normotensive volunteers, digital blood pressure was determined, and the value was compared to direct brachial arterial pressure and to that measured by a conventional, indirect Korotkoff-method in the upper arm. The correlation coefficient was determined by changing blood pressure with intravenous administration of vasoconstrictors, sublingual nitroglycerin, and stress tests. Although the absolute value of the digital blood pressure was slightly lower than direct arterial pressure, the correlation between the two determinations was highly significant. The difference in readings between direct and digital arterial pressure was not significant even when the pressure was fluctuated with administration of vasoactive drugs and stress tests. In 2 of 6 volunteers the photosignals of the digital arterial pulses became too small to measure pressure 30 min after they entered in a cold room. However, the digital/brachial blood pressure difference did not alter even when the signals became small during the cold exposure in the remaining 4 subjects. Afterward, the subjects visited our outpatient clinic, where their digital blood pressure was taken. The value was compared with the indirect, contralateral brachial blood pressure. The absolute difference between the readings increased significantly when hypertension advanced. Among the patients (WHO, stage I) treated with antihypertensive drugs, the digital/arm pressure gap was the greatest in patients treated with beta-adrenergic blockers, diuretics and calcium channel blockers in decreasing order. These results indicate that digital blood pressure is influenced by the severity of hypertension and drugs; i.e., hypertensive vascular injury and/or atherosclerosis lowers the peripheral blood pressure leading to impaired peripheral tissue perfusion in the hypertensive patient, and beta-adrenergic blockers may deteriorate peripheral circulation in spite of their hypotensive effects.
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PMID:Measurement of digital arterial pressure in patients with essential hypertension. 236 7

Calcium channel blocking drugs, or "calcium antagonists", have been increasingly used in the last decade, both as valuable cardiovascular drugs, and as tools to investigate the pharmacology of the calcium channels which play a vital role in the excitation-activation coupling of many excitable cells. Three important developments, "patch clamping" to investigate single calcium channels, ligand binding studies to investigate the calcium antagonist "receptor sites", and the introduction of novel calcium channel activators, or "calcium agonists", have recently led to greater understanding of the mechanism of action of drugs on the calcium channel. We show here how the calcium channel modulators interact with the binding sites to increase or decrease calcium flux, and hence to modulate the activity of many excitable tissues. We predict that these new developments will soon result in the isolation of purified calcium channels, and investigation of their subtypes and drug sensitivities. This information could lead to the introduction of novel, more selective calcium antagonists for a variety of indications such as atherosclerosis or neurological disorders. Of particular interest is the potential of tissue-selective calcium agonistic drugs to combat cardiac failure or endocrinological disorders.
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PMID:Modulation of calcium channel function by drugs. 241 32

Proliferation and migration of smooth muscle cells (SMCs) in the arterial wall may play a role in the development of atherosclerosis and hypertension. If cell migration and proliferation are dependent on extracellular calcium, then treatment with calcium channel blockers such as nitrendipine may alter these cellular responses. In the studies reported here, proliferation and migration activities were assessed in cultured bovine carotid artery smooth muscle cells exposed to nitrendipine. SMCs in long-term culture are characterized by periods of either stable or enhanced proliferative activity. During the stable periods, 1 microM nitrendipine has no effect on proliferation, but during periods of enhanced proliferation, 1 microM nitrendipine augments growth by approximately 20%. SMC migration rates and interdivision times were determined from analysis of time-lapse cinematography films. During stable periods of growth, cell migration rate was inversely related to interdivision time (i.e., fast migrating cells had the shortest interdivision times). Treatment with 1 microM nitrendipine abolished the relationship between migration rate and interdivision time and prolonged interdivision times. These data suggest that the ability of nitrendipine to alter SMC proliferation, interdivision time, and migration is dependent upon the overall proliferative state of the culture.
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PMID:Effects of nitrendipine on growth activity in cultured vascular smooth muscle cells. 246 48

Atherosclerosis is an arterial disease characterized by focal accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolic function. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium channel blockers can reduce the accumulation of atherogenic lesion components and thus apparently decrease the progression of lesions. Although there are some conflicting data in the animal model studies using calcium channel antagonists, as a result of differences in experimental designs, it is now apparent that several classes of calcium channel blockers inhibit the progression of early arterial lesions induced by cholesterol feeding. The dihydropyridine calcium channel blockers appear to be more potent antiatherosclerotic agents than other classes of calcium channel antagonists. Several mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolic functions may be responsible for the calcium channel blocker effects on early lesion progression. For example, recent studies in cell culture model systems suggest that calcium channel blockers may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium channel blockers may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium-independent metabolic activities.
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PMID:The antiatherogenic potential of calcium antagonists. 246 1

Experimental research using in vitro and in vivo models of vascular injury have delineated several common mechanisms that characterize the arterial damage in diseases such as atherosclerosis and hypertension. Changes in endothelial permeability, smooth muscle cell proliferation, and accumulation of connective tissue matrix are major common mechanisms. Chronic hyperlipidemia is a major determinant of the proliferative arterial lesions in atherogenic models. Calcium antagonists of very diverse structure and function have been shown to have antiatherogenic potential in several animal model systems of arterial injury. Calcium channel-blockers of several chemical classes have been demonstrated to alter endothelial function, intimal smooth muscle proliferation, and lipid accumulation in the arterial wall. Cell culture model systems have elucidated several potential mechanisms that may contribute to the antiatherogenic potential of the calcium channel-blockers. These activities may in part involve protection of arterial cells from calcium overload via inhibition of calcium flux across voltage-regulated ion channels. However, other activities of these drugs, such as inhibition of cholesterol esterification and matrix protein formation, appear to function independently of calcium flux. A hypothesis is presented that lipophilic calcium channel-blockers are accumulated in cell membranes and perturb metabolic function as a result of altering local membrane structure.
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PMID:Protective action of calcium channel antagonists in atherogenesis and experimental vascular injury. 264 20

Atherosclerosis is an arterial disease characterized by localized accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolism. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium antagonists can reduce the accumulation of atherogenic lesion components and decrease the progression of lesions. Although there are some conflicting data in the animal model studies, it is now apparent that several classes of calcium antagonists inhibit the progression of early arterial lesions induced by cholesterol-feeding in animals. The dihydropyridine class of calcium antagonists may be more potent as anti-atherosclerotic agents than the other classes. Mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolism may be responsible for the effects of calcium antagonists on early lesion progression. Recent studies in cell culture-model systems suggest that calcium antagonists may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by arterial wall cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium antagonists may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium channel-independent metabolic activities, which affect lesion development.
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PMID:Antiatherogenic properties of calcium antagonists. State of the art. 265 28

The effect of endothelin (ET), a novel endothelium-derived vasoconstrictive peptide, on DNA synthesis was studied in cultured rat vascular smooth muscle cells (VSMC). ET stimulated incorporation of [3H]thymidine into DNA of the quiescent VSMC in a dose-dependent manner; the approximate half-maximal and maximal stimulation for DNA synthesis was induced with 2 x 10(-10) M and 10(-9) M, respectively. The stimulatory effect by ET on DNA synthesis was completely inhibited by the calcium channel blocker nifedipine. ET combined with epidermal growth factor and transforming growth factor-alpha, but not with platelet-derived growth factor, had synergistic effects. These data indicate that ET is a potent mitogen as well as a constrictor for VSMC, suggesting its potential role in the development of vascular disease.
Atherosclerosis 1989 Aug
PMID:Endothelin is a potent mitogen for rat vascular smooth muscle cells. 267 59

Since hypertension is an important risk factor for atherosclerosis, it is logical to assume that treatment to lower blood pressure will prevent atherosclerosis. However, the relationship between hypertension and atherosclerosis is indirect and complex. Drugs that lower pressure will prevent heart failure and arteriolar complications such as renal failure or strokes caused by lacunar infarction or brain haemorrhage due to rupture of microaneurysms. However, there is little evidence that atherosclerotic complications can be reduced by lowering pressure. It is important to understand the pathogenesis of atherosclerosis and its complications, which are related to lipoproteins and arterial flow disturbances, in order to develop an approach to selecting those antihypertensive drugs which may prevent atherosclerotic complications related not only to initiation and progression of atherosclerotic plaques, but to the embolisation of platelet clumps or atherosclerotic debris, or events such as intraplaque haemorrhages, that lead to myocardial or cerebral infarction. Antihypertensive drugs have different effects on lipoproteins and on arterial flow disturbances that may have important implications for prevention. Alpha-blockers and drugs with beta 2 agonist activity have beneficial effects on lipoprotein profiles, ACE inhibitors and calcium channel antagonists have some anti-atherosclerotic effects in animal models, while beta-blockers have beneficial effects on flow disturbances and are anti-atherosclerotic in animal models and man. Future studies to determine how to prevent atherosclerotic complications in hypertensive patients will require methods for noninvasive measurement of atherosclerosis.
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PMID:Pathogenesis of atherosclerosis and its complications: effects of antihypertensive drugs. 269 95

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


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