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

It has recently been shown that human red blood cells possess a voltage-independent calcium channel which can be influenced by in vitro modification of the membraneous cholesterol content. To determine whether there is also a link between plasma lipids and the calcium influx through this channel under in vivo conditions, the calcium influx was measured in red blood cells from 51 male donors (aged 41 +/- 5 years). The influx through the channel was defined as the nitrendipine (15 mumol/l)-inhibitable part of 45Ca2+ influx. The Ca(2+)-ejecting ATPase was inhibited by vanadate. The results demonstrate a strong inverse relationship (r = -0.81; P < 0.001) between the plasma concentration of high density lipoproteins (HDL) and 45Ca2+ influx. No significant correlation was found between 45Ca2+ influx and triglycerides, low density lipoproteins (LDL), very low density lipoproteins (VLDL), total plasma cholesterol or extracellular electrolytes (K+, Na+, Ca2+, Mg2+). The results indicate that HDL are involved in the modulation of the calcium channel and provide a link between the cellular cholesterol turnover and the calcium influx in the pathogenesis of atherosclerosis and hypertension.
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PMID:High density lipoproteins--modulators of the calcium channel? 285 25

This paper reviews published data concerning the effects of antihypertensive drugs on the development of atherosclerosis in experimental animal models with hyperlipoproteinaemia. Emphasis is placed on the influence of calcium channel antagonists on this process, and the potential mechanisms responsible for the effect. In addition, studies of the action of beta-receptor antagonists on atherogenesis are also summarized. The results indicate that several antihypertensive drugs may inhibit or retard experimentally-induced atherogenesis, even in normotensive animals, although the mechanisms for the effects remain poorly understood.
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PMID:Effects of calcium channel antagonists and other antihypertensive drugs on atherogenesis. 289 19

Drugs influencing calcium metabolism in animals fed high-fat diets may modify the progression of atherosclerosis. Agents that enhance calcium transport (catecholamines, vitamin D, parathyroid hormone) may accelerate atherogenesis. Conversely, agents with calcium chelating (diphosphonic acid and thiophene carboxylic acid derivatives), calcium channel blocking (dihydropyridine derivatives, verapamil and its derivatives, diltiazem), and anti-adrenergic (beta-blockers) properties have been demonstrated to suppress atherogenesis in rabbits and monkeys. Possible mechanisms of action include lowering of arterial pressure, minor changes in circulating lipoproteins, altered receptor-dependent lipoprotein uptake and lipoprotein metabolism, inhibition of cell migration and cell proliferation, and non-specific protection of injured cells in atheromatous lesions.
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PMID:Anti-atherosclerotic effects of calcium antagonists: a brief review. 332 99

Several lines of evidence, including the reported ability of calcium channel blockers to prevent atherogenesis in cholesterol-fed rabbits, suggest that calcium mediates one or more of the pathologic changes in atherosclerosis. Moreover, it has long been known that calcium accumulates in atherosclerotic blood vessels. To test the hypothesis that a substantial fraction of this accumulated calcium is intracellular and to identify possible causes of this accumulation, calcium fluxes and contents were determined in aortic segments from cholesterol-fed rabbits and age-matched controls. A new method, based on 45Ca efflux experiments and computer-assisted kinetic analysis, was used to measure intracellular and extracellular calcium contents (nmol calcium/g wet wt tissue) and fluxes. Total intracellular calcium increased from 269 +/- 11.6 to 1,300 +/- 352 nmol/g in cholesterol-fed animals compared with controls (p less than 0.01). This change was sufficient to account for the observed increase in total tissue calcium from 4,190 +/- 211 to 5,240 +/- 477 nmol/g (p less than 0.05). Thus, the fraction of tissue calcium that is intracellular increased significantly from 0.065 +/- 0.006 to 0.223 +/- 0.048 (p less than 0.01) in experimental atherosclerosis. In addition, the data were quantitatively consistent with the hypothesis that these changes are brought about by a 4.8-fold increase in the plasma membrane calcium permeability of aortic smooth muscle cells. These results provide evidence that increased intracellular calcium is a possible mediator of cholesterol-induced atherogenesis.
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PMID:Evidence for increased aortic plasma membrane calcium transport caused by experimental atherosclerosis in rabbits. 333 59

Data relating to the effects of calcium channel blockers on experimental atherosclerosis in rabbits are inconsistent with most studies finding no effect on either serum lipids or atherosclerosis. We have administered flordipine (5, 15 or 45 mg/kg/day) for 10 weeks to rabbits fed 1% cholesterol and 4% corn oil. At no level of treatment was there an effect on serum or liver lipids or on aortic sudanophilia.
Atherosclerosis 1988 Jan
PMID:Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits. 335 10

The events involved in atherogenesis include platelet deposition on damaged endothelial surfaces; migration and proliferation of smooth muscle cells; the formation of elastin, collagen, and glycosaminoglycans, followed by the penetration and complexing of lipoproteins; and, calcification. Since calcium is involved in these and other events, considerable data exist on the effects of altering calcium influx in experimental atherosclerosis. Interventions that increase calcium deposition tend to increase the severity of experimental atherosclerosis, whereas interventions that reduce calcium entry into cells tend to reduce its progression. Using rabbits, researchers have recently focused on the ability of calcium channel blockers, such as nifedipine, verapamil, and diltiazem, to attenuate the development of experimental atherosclerosis. Studies also suggest that although calcium channel blockers may protect against the development of experimental atherosclerosis, they are less effective in inducing its regression. Further, studies with calcium channel blockers in rabbits deficient in low-density lipoprotein receptors did not show protection against the development of atherosclerosis. However, no clinical studies are yet available to judge the potential protective effects of calcium channel blockers in humans. Since many patients are now receiving long-term calcium blocker therapy for hypertension, these findings may be relevant in the selection of antihypertensive therapy, provided that protective effects can be demonstrated.
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PMID:Calcium channel blockers and atherogenesis. 355 1

The effects of histamine on coronary vasomotor tone and on myocardial blood flow distribution were studied in the anaesthetised rabbit in the absence of histamine H1-receptor blockade and calcium channel blockade. Two groups of rabbits were used, those fed a normal diet and those fed a high cholesterol diet (2%) for 8 to 12 weeks. Continuous recordings of standard limb lead electrocardiograms (ECG) were obtained, and all animals were pretreated with cimetidine, an H2-receptor blocker, to minimise the intervening systemic effects of histamine. In the absence of H1-receptor blockade, histamine produced a marked (40 to 50%) reduction in coronary blood flow without significantly affecting other cardiovascular variables. This effect was seen uniformly across the free wall of the left ventricle, ie endo-epi flow ratios did not significantly change. Concomitant with the coronary vasoconstriction were significant depressions (greater than or equal to 0.1 mV) of the ECG ST-segment and elevation of cardiac tissue lactate and lactate:pyruvate ratio. These histamine-mediated responses were independently abolished by chlorpheniramine (1.5 mg X kg-1 iv) and verapamil (0.5 mg X kg-1 iv). Atherosclerosis reduced the average dose of histamine needed to induce these ischaemic changes from 55 +/- 6 to 34 +/- 6 micrograms X kg-1 X min-1 (p less than 0.05). These findings suggest that in the H2-receptor blocked rabbit coronary vascular bed histamine causes tissue ischaemia by an H1-receptor mechanism. The decrement in myocardial blood flow appears to involve activation of plasma membrane calcium channels and is sensitive to atherosclerosis.
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PMID:Evidence of histamine-induced myocardial ischaemia: reversal by chlorpheniramine and potentiation by atherosclerosis. 408 32

In order to study the influence of the cholesterol content on the calcium entry channel, the human red blood cell was used as a model system. The cholesterol to lecithin ratio (C/L ratio) of the membrane was modified experimentally by incubating the cells (15h, 25 degrees) with liposomes of defined C/L ratios. Subsequently, net 45Calcium-influx into the cell was measured by inhibiting the Ca-ejecting ATPase with vanadate. Additionally, the use of nitrendipine, a potent calcium channel inhibitor, during incubation allowed the determination of Ca-influx through the calcium channel. A positive correlation between the 45Ca++-influx and the molar C/L ratio of the membrane was found over a wide C/L range. A molar C/L ratio of 1.4 in the membrane increased calcium influx by 150 % compared to controls (molar C/L ratio = 0.8, calcium influx rate = 100 %), while a molar C/L ratio at less than 0.75 decreased calcium influx by 50 %. We conclude, that the cholesterol content of the membrane greatly influences the calcium channel and thus plays a pivotal role for the availability of calcium as a second messenger. These findings may provide a link between high plasma cholesterol and the development of atherosclerosis as well as enhanced platelet aggregability.
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PMID:The cholesterol content of the human erythrocyte influences calcium influx through the channel. 609 23

Changes due to aging of the cardiovascular system play an important role in the development of hypertension and its complications in the elderly. As shown in recent experimental studies in rats, the arterial changes that normally take place resemble those resulting from hypertension. They may be preventable by maintenance of low blood pressures and may be secondary to prolonged hemodynamic effects on the artery wall. The major hemodynamic consequences of aging in man include an increase in total peripheral vascular resistance, which occurs as a result of both arterial and arteriolar disease. Other features with potentially important therapeutic implications in the elderly include an increased tendency for left ventricular dysfunction and cardiac arrhythmias, decreased baroreceptor sensitivity, and atherosclerosis-induced reduction of blood flow to vital organs. Older patients also tend to have a reduced fluid volume and an abnormal distribution and metabolism of drugs. These factors lead to greater sensitivity to potential side effects and, thus, greater difficulty in managing their hypertension. Diuretics, beta blockers, and calcium channel blockers appear to be the most useful initial antihypertensive drugs in the elderly. The cardioprotective effects of beta blockers and the desirable hemodynamic action of calcium antagonists provide compelling justification for their use in many patients. Centrally acting sympatholytic drugs such as methyldopa, clonidine, and guanabenz are useful as second-step agents, usually in combination with a diuretic. In the presence of moderate to severe diastolic hypertension, hydralazine, captopril, and minoxidil may have value, but such potent agents should generally be avoided with isolated systolic hypertension. In elderly hypertensive patients with other complicating diseases, sufficient alternative treatment options are now available to allow tailoring of therapy to the special needs of each patient, thereby minimizing adverse reactions to therapy. However, relatively low doses of medications and conservative therapeutic objectives are usually necessary, particularly in patients with isolated systolic hypertension in whom the benefits of treatment are still to be determined.
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PMID:Treatment of the elderly hypertensive patient. 614 85

Clinical and autopsy studies indicate that most patients who present with unstable angina or an acute myocardial infarction (AMI) have significant underlying coronary atherosclerosis. This review discusses 4 mechanisms that may contribute to the precipitation of these acute ischemic clinical syndromes: progression of atherosclerosis, acute coronary thrombosis, coronary artery spasm, and platelet aggregation. Numerous clinical trials using thrombolytic agents early during AMI have shown the incidence of thrombosis to be at least 60%. Other studies suggest that platelet aggregation frequently contributes to the evolution of AMI from unstable angina and that spasm may occasionally play a similar role. The therapeutic implications of these mechanisms are also considered in light of their potential to restore coronary artery blood flow (vs conventional methods thought mainly to reduce myocardial oxygen demand) and thereby limit the infarct process. The role of vasodilators, thrombolytic agents, antiplatelet drugs and beta-adrenergic blocking drugs are discussed. Finally, therapeutic guidelines for the treatment of acutely ill patients are constructed that emphasize the need for a comprehensive yet time-efficient treatment strategy that uses nitrates, calcium channel-blocking drugs, streptokinase, heparin, aspirin and, in selected patients in an unstable condition, emergency percutaneous transluminal coronary angioplasty and coronary artery bypass grafting.
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PMID:Mechanisms contributing to precipitation of unstable angina and acute myocardial infarction: implications regarding therapy. 615 Jun 30


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