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

The limitations of medical treatment in angina pectoris depend on its efficacity and indications. 1. Efficacity of medical treatment.--Anti-anginal drugs are able to relieve anginal pain in at least 3/4 of cases. However, the ability of medical measures (diet, exercise, stopping smoking, hypolipidemic drugs, antihypertensive drugs, anticoagulants, platelet anti-aggregants, antiarrhythmics, inotropic agents, vasodilators and diuretics) to prevent coronary atherosclerosis delay its progression and prevent its complications--so increasing the life expectancy of coronary patients--remains very uncertain. 2. Frontiers and judications of medical treatment.--Coronary patients with few or no symptoms appear to be best suited for long-term anti-anginal treatment with long acting nitrate derivatives and/or betablockers. The ability of the latter group to increase the life expectancy of all coronary patients remains to be shown. The limits of the indications of medical treatment are more difficult to define either by purely subjective criteria (incapacitating angina after trials of anti-anginal drugs at adapted doses) or by "objective" criteria (ergometry, coronary angiography).
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PMID:[The limits of the medical treatment of angina pectoris]. 613 4

Management of patients with concomitant hypertension and angina pectoris mandates that the physician pay attention to the underlying pathophysiology. The heart, when exposed to years of hypertension, becomes "remodeled." Overall mass is enlarged, the walls are thickened, and initial cavity volume remains normal or relatively small. Left ventricular end-diastolic pressure rises in the setting of a hypertrophic noncompliant ventricle; coronary resistance and coronary perfusion pressure are increased; and coronary vascular reserve, even with widely patent coronary arteries, is decreased. Long-standing hypertension--a risk factor for coronary atherosclerosis--is often accompanied by epicardial coronary stenoses that aggravate these coronary abnormalities. In managing the patient with hypertension and angina pectoris, it is important to determine whether the angina occurs in the setting of hypertensive hypertrophic disease alone or coexists with coronary arterial stenoses. Also important to therapy is whether the ventricle is of normal size with good function or decompensated with dilatation and diminished function. The latter two anatomic considerations, namely, epicardial coronary patency and left ventricular cavity size, will influence the choice of an anti-ischemic regimen. For example, diuretic and nitrate therapy can be hazardous, and digitalis unnecessary, in the setting of a nondilated hypertrophic ventricle with hyperdynamic function. On the other hand, the combined use of beta blocking agents plus calcium antagonists is particularly effective in lowering blood pressure and in improving coronary blood flow. Finally, this combination has been shown to be rapidly effective and to have prolonged benefit in this setting. The choice of these latter agents is also affected by the underlying state of the ventricle. Calcium channel blocking agents without significant negative inotropic effect, such as nifedipine and nitrendipine, would be suitable in patients with decompensated ventricular function and dilated left ventricular cavities. Both of these drugs have been shown to increase cardiac output and contractility via a reflex effect and to have little or no direct negative inotropic effect. In contrast, verapamil has a direct negative inotropic effect. The final choice of agents must be tailored to the needs of the individual patient, and the physician also has to determine the role of specific agents in the natural history of hypertensive heart disease.
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PMID:Management of patients with hypertension and angina pectoris. 614 86

We wished to determine whether long-term treatment with organic nitrovasodilators has pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in cholesterol-fed rabbits. For 15 weeks, six groups of 9 New Zealand White rabbits received a standard diet, which contained no admixture, pentaerythrityl-tetranitrate (PETN 6 mg/kg body weight/day), or isosorbide-5-mononitrate (ISMN 2 mg/kg body weight/day). In the other three groups, the same diets were further enriched with cholesterol (0,75%). Four rings of thoracic aorta were used for tension studies; these rings and the aortas from the aortic arch to bifurcation were then fixed in formol and stained with Sudan IV to determine the area of luminal atherosclerotic lesions by a computerized laser-scanning approach. The cholesterol diet increased plasma levels of cholesterol from 69.8 +/- 10.4 to 907.1 +/- 85.5 mg/dl. A similar result was obtained in the group receiving PETN/cholesterol, but the group fed ISMN/cholesterol showed a significantly higher plasma level of cholesterol (1,165 +/- 81.4 mg/dl). Plasma levels of PETN metabolites were still detectable by gas chromatography/mass spectrometry after a 24-h in vivo washout period. The cholesterol diet induced a pronounced degree of atherosclerotic lesions in the aortic arch and the thoracic and abdominal aorta: 73.3 +/- 1.9, 46.3 +/- 2.5, and 49.6 +/- 3.6%, respectively. Additional treatment with PETN resulted in a reduction of this atherosclerotic area to 58.6 +/- 2.05% (p < 0.0001), 34.7 +/- 1.98% (p < 0.01), and 39.3 +/- 3.06% (p < 0.05). In contrast, ISMN had no significant effect on this parameter. The cholesterol diet also induced an endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine (ACh). Treatment with PETN completely inhibited the development of endothelial dysfunction, whereas ISMN had no effect. In the three groups receiving a cholesterol diet, an increased extent of aortic lesions significantly correlated with increased endothelial dysfunction measured in the same preparations. The long-term treatment with PETN did not affect the vasorelaxing potency of PETN in aortic rings, and similar results were obtained in the case of ISMN. We conclude that long-term treatment with doses of PETN, which do not promote the development of in vitro vascular nitrate tolerance, may protect against atherosclerosis and endothelial dysfunction. This novel, yet unknown pharmacodynamic quality of nitrovasodilators like PETN may contribute to their long-term efficacy in coronary artery disease but may also imply new therapeutic indications in the future.
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PMID:In vivo effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate on the development of atherosclerosis and endothelial dysfunction in cholesterol-fed rabbits. 754 71

Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments NO release in PMW. We determined serum levels of nitrite/nitrate (NO2 + NO3) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW. One group (HRT-PMW, n = 13) received continuous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n = 13) did not receive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling. Serum NO2 + NO3 levels increased in HRT-PMW for the duration of the study, whereas serum NO2 + NO3 levels remained unchanged in control PMW. When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change in NO2 + NO3 levels in HRT-PMW was significantly greater compared with the change in control PMW (P = .037). Likewise, when only those samples collected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO2 + NO3 levels in the HRT-PMW group remained significant (P = .047) compared with control PMW.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study. 772 43

Nitric oxide (NO) synthesised by endothelial cells, plays a key role in the control of vascular tone. Its synthesis from L-arginine is assured by NO-synthase, the activity of which is dependent on intracellular calcium concentrations, which are themselves modulated by pharmacological (acetylcholine, serotonin, bradykinin...) or physical factors (shearing forces exerted by blood flow). NO acts by stimulating a soluble guanylate-cyclase of the smooth muscle cells in the vessel wall. Its vasodilator effect is therefore mediated by an increase in intracellular cyclic GMP concentration. The synthesis or liberation of NO by the endothelium may be decreased or abolished during many pathological processes (hypercholesterolaemia, atherosclerosis, systemic or pulmonary hypertension...). The significance of this abnormality of NO-mediated endothelium-dependent vasodilation in different pathological conditions has not been established. However, it is probably significant in view of the different properties of NO: vaso-relaxation, antiaggregant and inhibition of vascular smooth muscle growth. It is not yet known whether this abnormality is a cause or a consequence of the underlying disease. From the therapeutic point of view, NO is an active metabolite of nitrate derivatives, sodium nitroprussiate and molsidomine which therefore share the same mode of action as the so-called "endothelium-dependent" vasodilatoe agents. The inhalation of NO, which is increasingly used in neonatal and adult intensive care units, is an alternative therapeutic approach in many conditions associated with pulmonary hypertension.
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PMID:[Nitric oxide, from vascular physiology to therapeutics]. 778 35

Cardiovascular diseases are the most important cause of mortality in industrialised countries. Contrary to cancer research, cardiovascular research mostly ignores toxic effects, apart from nicotine, caffeine, alcohol, a few pharmaceutical drugs, and the (in our countries) minor workplace problems carbon disulfide, nitrate esters, and carbon monoxide. But many workplace chemicals are known to be harmful to the cardiovascular system; beside the mentioned, also organic solvents, metals, pesticides, vinyl chloride, polychlorinated biphenyls, etc. Several toxic mechanisms in the cardiovascular system are already known: e.g., long-term development of atherosclerosis, hypertension, coronary heart disease, cardiomyopathy, and arrhythmia. To neglect cardiovascular toxicity is contrary to logic; for many cardiovascular diseases toxic effects may be constitutive; more of these effects may be seen in the future.
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PMID:[Do workplace chemicals harm the heart?]. 832 24

The endothelium modulates vascular tone by releasing NO, which is a potent vasodilator and inhibitor of platelet aggregation. Thus, the endogenous nitrate has an important protective role in preventing vasospasm and thrombus formation. In addition, the endothelium is a source of contracting factors, such as endothelin-1. Due to its strategical anatomic position, the endothelium is a primary target for injurious stimuli and cardiovascular risk factors. Oxidized LDL reduce the endothelial production of NO and enhance that of endothelin-1. The same pattern of endothelial dysfunction occurs in hypercholesterolemia and in part in atherosclerosis. These alterations of endothelial function may contribute to vasospasm and thrombus formation, which are common events in patients with atherosclerosis.
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PMID:Endothelium-derived nitric oxide, endothelin, and platelet vessel wall interaction: alterations in hypercholesterolemia and atherosclerosis. 835 62

This review discusses the mechanisms of action of the organic nitrates, nitrate tolerance, and the effects of nitrates in patients with stable angina pectoris. The nitrates are prodrugs that enter the vascular smooth muscle, where they are denitrated to form the active agent nitric oxide (NO). NO activates guanylate cyclase, which results in cyclic guanosine monophosphate (cGMP) production and vasodilation as a result of reuptake of calcium by the sarcoplasmic reticulum. NO is identical to endothelium-derived relaxing factor (EDRF), which induces vasodilation, inhibits platelet aggregation, reduces endothelium adhesion, and has anticoagulant and fibrinolytic effects. Thus, the nitrates may be more than vasodilators and, in addition to reducing ischemia, may affect the process of atherosclerosis. The vascular effects of nitrates are attenuated during sustained therapy. Although the basis for the phenomenon of nitrate tolerance is not completely understood, sulfhydryl depletion as well as neurohormonal activation and increased plasma volume may be involved. The administration of N-acetylcysteine, angiotensin-converting enzyme (ACE) inhibitors, or diuretics do not consistently prevent nitrate tolerance. At present, intermittent nitrate therapy is the only way to avoid nitrate tolerance. The intermittent administration of nitrates, however, cannot provide continuous therapeutic benefits, and thus monotherapy with nitrates is not suitable for many patients with stable angina pectoris.
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PMID:Nitrates and angina pectoris. 837 99

Estradiol is known to exert a protective effect against the development of atherosclerosis, but the mechanism by which this protection is mediated is unclear. Since animal studies strongly suggest that production of endothelium-derived relaxing factor is enhanced by estradiol, we have examined the effect of estrogens on nitric oxide (NO) synthase (NOS) activity, protein, and mRNA in cultured bovine aortic endothelial cells. In reporter cells rich in guanylate cyclase, it has been observed that long-term treatment (> or = 24 hr) with ethinylestradiol (EE2) dose-dependently increased guanylate cyclase-activating factor activity in the conditioned medium of endothelial cells. However, conversion of L-[14C]arginine to L-[14C]citrulline by endothelial cell homogenate or quantification of nitrite and nitrate released by intact cells in the conditioned medium did not reveal any change in NOS activity induced by EE2 treatment. Similarly, Western and Northern blot analyses did not reveal any change in the endothelial NOS protein and mRNA content in response to EE2. However, EE2 dose- and time-dependently decreased superoxide anion production in the conditioned medium of endothelial cells with an EC50 value (0.1 nM) close to that which increased guanylate cyclase-activating factor activity (0.5 nM). Both of these effects were completely prevented by the antiestrogens tamoxifen and RU54876. Thus, endothelium exposure to estrogens appears to induce a receptor-mediated antioxidant effect that enhances the biological activity of endothelium-derived NO. These effects could account at least in part for the vascular protective properties of these hormones.
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PMID:Ethinylestradiol does not enhance the expression of nitric oxide synthase in bovine endothelial cells but increases the release of bioactive nitric oxide by inhibiting superoxide anion production. 863 24

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for >100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.
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PMID:Beneficial actions of nitrates in cardiovascular disease. 863 24


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