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)

The aim of the work was to study the effect of 8-week treatment with two calcium channel blockers on some parameters of lipid metabolism in rabbits. Experimental atherosclerosis was induced by 1% cholesterol diet. The calcium channel blockers were administered twice daily in the following doses: nifedipine 1.0 mg.kg-1 and verapamil 2.0 mg/kg-1 x day-1. The treatment with calcium channel blockers enhanced the level of total cholesterol as well as of triglycerides and decreased the HDL: total cholesterol ratio in all the experimental groups. The changes induced by nifedipine were, however, less significant compared to the effect of verapamil. The absolute amount of fatty acids determined by gas chromatography was lower after nifedipine administration in comparison to the verapamil treated group. Nifedipine induced a more favorable proportion in the composition of fatty acids. The increase in the level of monounsaturated fatty acids (palmitoleic and oleic acid) as well as the decrease in the level of polyunsaturated fatty acids (especially linoleic acid) was the lowest in the nifedipine treated group. (Fig. 6, Ref. 30.).
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PMID:[Comparison of the effect of nifedipine and verapamil on lipid metabolism in experimental atherosclerosis in rabbits]. 129 Oct 43

Recent clinical studies have shown that calcium channel blockers can retard and possibly reduce the angiographic progression of coronary artery disease. Calcium channel blockers also inhibit dietary-induced atherosclerosis in animal models of this disease. In this study, we delineate potential cellular and molecular mechanisms by which nicardipine, a dihydropyridine calcium antagonist, may alter lipoprotein and cholesterol trafficking, affect the regulatory signal transduction pathways involved in accelerating cholesteryl ester (CE) catabolism in vascular smooth muscle cells, and modulate cell-cell interactions of vascular and inflammatory cells. We demonstrate in arterial smooth muscle cells that nicardipine increases 1) LDL binding, uptake, and degradation, 2) RNA transcript levels for the LDL receptor, 3) CE catabolic activity, 4) PGI2 release, and 5) RNA transcript levels for cyclooxygenase. Furthermore, nicardipine blocked cytokine-induced monocyte adhesion to endothelial cells and smooth muscle cells. Taken together, these findings support the hypothesis that nicardipine may function as an anti-atherosclerotic agent by promoting CE catabolism and cholesterol clearance and by reducing monocyte adhesion to the activated endothelium.
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PMID:Dihydropyridine calcium antagonist modulates cholesterol metabolism and eicosanoid biosynthesis in vascular cells. 131 89

Calcium channel blockers have been shown to retard the development of atherosclerosis in rabbits fed cholesterol-rich diets. The mechanism accounting for this effect is controversial but may be by stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, by amelioration of hypercholesterolemia-induced endothelial dysfunction, or by inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in two clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, nicardipine-treated patients experienced significantly less progression of minimal lesions, defined as stenoses of < or = 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy, nifedipine had no effect on overall progression and regression but reduced the rate of appearance of new coronary lesions. These studies constitute a potentially important new approach to the management of coronary atherosclerosis.
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PMID:Interventions that beneficially influence the evolution of coronary atherosclerosis. The case for calcium channel blockers. 142 44

Hypertension is a constellation of abnormalities, including metabolic disorders. The current approach to treatment of hypertension should not be dictated solely by measures to lower blood pressure. It must also take into consideration the effect of antihypertensive drug treatment on the development of atherosclerosis and many other important factors. Evidence from rabbit models and cell cultures indicates that calcium channel blockers are antiatherogenic through a variety of mechanisms. In addition to preserving endothelial function, these agents inhibit the following: Platelet aggregation Migration of monocytes and smooth-muscle cells into the intima Incorporation of low-density lipoprotein cholesterol into these cells Matrix formation Calcium overload in atherosclerotic lesions However, additional studies are needed to delineate the antiatherogenic effects of these and other antihypertensive agents.
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PMID:Antiatherosclerotic effects of calcium channel blockers. 149 83

Hypertension should be detected and treated early in diabetic patients. It markedly affects the morbidity and mortality of diabetic individuals as a result of both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. No prospective studies have addressed the effects of antihypertensive regimens on the incidence of congestive heart failure, stroke, and coronary artery disease in large groups of diabetic patients. Such studies are urgently needed. Special consideration should be given to the effects of antihypertensive drugs on glycemic control and the lipid profile of the diabetic patient. Because hyperinsulinemia (and insulin resistance) have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may become an important element in the selection an antihypertensive agent. More information, however, is needed in these areas. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer a more favorable metabolic profile as compared with diuretics and beta-blockers. The former agents should be used as initial drugs in most clinical settings.
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PMID:Management of hypertension in diabetes. 161 71

There is evidence that calcium antagonists (calcium channel blockers) may suppress atheroma formation in animals fed high-fat diets. Studies on the antiatherosclerotic effects of calcium blockers have suggested a variety of possible mechanisms: (a) lowering of arterial pressure, (b) decrease in atherogenic plasma lipoproteins, (c) suppression of accumulation of intracellular lipids, (d) suppression of atherogenic platelet dysfunction, (e) prevention of dyslipidemic endothelial injury, (f) inhibition of chemotaxis and cell migration, (g) inhibition of cell proliferation, (h) inhibition of deposition of matrix proteins, (i) suppression of tissue mineralization, and (j) retardation of cell necrosis. Although it is tempting to ascribe the antiatherosclerotic effects of calcium blockers to a blockade of calcium channels, other possible common mechanisms of action involving low-affinity drug-binding sites must be considered. Recently, two randomized, prospective clinical trials designed to determine the effects of calcium channel blockers on the progression of coronary artery disease have been completed. Results of the trials suggest that calcium channel blockers suppressed the progression of coronary atherosclerosis. The utility of calcium channel blockers for the treatment of atherosclerosis will require further evaluation.
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PMID:Calcium channel blockers and atherosclerosis. 170 8

Many detailed studies have demonstrated that calcium antagonists can suppress development of diet-induced atherosclerosis in the thoracic aorta of animals. A number of possible mechanisms have been proposed based on in vitro work, but the exact mechanism remains unclear. Alteration of serum lipid levels and blood pressure does not appear to be the common pathway. Differing effects between calcium antagonists of different classes indicate that the voltage-dependent calcium channel-blocking action common to all calcium antagonists is not the sole mechanism. Preliminary results of several major quantitative angiographic studies in human coronary artery disease have recently become available and indicate that calcium antagonists are able to retard the progression of existing lesions in humans also. There is also evidence that calcium antagonists may prevent the development of new lesions and, in some cases, induce lesion regression. Longer follow-up and further trials are required to assess the appropriateness of widespread clinical application of these agents in coronary artery disease, to determine the optimal timing for their introduction, and to define their mechanism of action in influencing the natural history of atherosclerosis.
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PMID:A review of calcium antagonists and atherosclerosis. 170 12

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
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PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50

Recent experimental and clinical studies suggest that structurally disparate calcium channel blockers retard the progression of atherosclerosis. However, mechanisms of action by which calcium blockers exert their antiatherosclerotic effects have not been completely elucidated. Formation of atherosclerotic lesions involves cells (macrophages, endothelial cells, and platelets) not expressing voltage-dependent (L-type) calcium channels, the major drug receptors for calcium channel blockers. Therefore, it is possible that these drugs act by non-L-type channel mechanisms. Recent reports indicate that nifedipine, verapamil, and diltiazem exert antiperoxidative effects on membrane lipids. It has been suggested that antiperoxidants such as probucol and butylated hydroxytoluene (BHT) exert antiatherosclerotic effects by preventing oxidation of low-density lipoprotein (LDL), a modification thought to confer atherogenic properties to the lipoprotein. Therefore, the beneficial effects of calcium channel blockers might be related to their antiperoxidative activity.
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PMID:Antiperoxidative actions of calcium antagonists and atherogenesis. 172 59

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide that can control local vascular tone, is the most potent of these factors. Of the three isoforms of endothelin, endothelial cells appear to release primarily endothelin-1. The peptide is formed from its precursor big endothelin via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to a specific receptor that activates phospholipase C and leads to the formation of inositol trisphosphate, diacylglycerol, and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to a voltage-operated calcium channel via a Gi protein. This may explain why calcium antagonists inhibit endothelin-induced contractions only in certain blood vessels. In the human forearm circulation, calcium antagonists of different classes prevent endothelin-induced contractions. In hypertension, the circulating endothelin levels appear to be normal, whereas the vascular sensitivity to the peptide is reduced in most vascular tissues, but normal and enhanced responses have also been reported. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are augmented, a phenomenon that may be related to an increased formation of the peptide induced by modified forms of low-density lipoproteins.
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PMID:Endothelin. 172 99


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