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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase-dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation.
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PMID:Endothelium-derived contracting factors. 173 45

Aspirin inhibits thromboxane A2 and prostaglandin formation in platelets and prostaglandin I2 (prostacyclin) in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in the arachidonic acid metabolism. Oral aspirin can be extensively hydrolyzed to inactive salicylate in the stomach and the liver (first-pass) before it enters the systemic circulation. Presystemic acetylation of platelets thus occurs during aspirin absorption, with a concomitant sparing of peripheral vascular cyclo-oxygenase, mainly exposed to salicylate. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long term aspirin treatment for secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. Combination of aspirin with streptokinase was significantly better than either drug alone. On the other hand two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for prevention of vascular disease.
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PMID:Aspirin as an antithrombotic drug: from the aggregometer to clinical trials. 215 Jul 36

The authors provide grounds for the principles of pathogenic therapy aimed at posthemorrhagic cerebral vasospasm, proliferation-necrotic angiopathy with ensuing cerebral damage wherein free radical oxidation and antifibrinolytic therapy are of major importance. The efficiency of combined pathogenic therapy comprising antioxidants, chelators, cyclooxygenase inhibitors, calcium antagonists, barbiturate protectors, membrane-stabilizing and limiting antifibrinolytic hemostatic drugs is evaluated.
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PMID:[Pathogenetic therapy of hemorrhagic strokes]. 217 81

Certain arachidonic metabolites may play a pathogenic role in psoriasis. Platelets are rich sources of 12-hydroxy-eicosatetraenoic acid (12-HETE) and thromboxane A2, mediators of skin inflammation and platelet aggregation, respectively. We have studied untreated psoriatic patients without a history of diabetes mellitus and smoking. In psoriatics, platelet aggregation elicited by thrombin, ADP, and ristocetin was significantly enhanced as compared with healthy adult volunteers. Enhancement of platelet aggregation was detected in patients with both minimal and widespread disease. The formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), a cyclooxygenase product, and 12-HETE, a 12-lipoxygenase product, was increased in psoriatics with widespread disease but not in those with minimal disease. Formation of 12-HETE was stimulated to a higher degree (125%) than HHT (98%) in psoriasis (P less than 0.05). Addition of platelet-derived 12-HETE to cultured human epidermal keratinocytes resulted in a stimulation of the DNA synthesis (68% at 10(-7) M). These data suggest that platelet activation occurs in psoriasis, and that release of inflammatory and mitogenic compounds by activated platelets may play a role in the pathophysiology of psoriasis. Whether enhanced platelet aggregation in psoriasis is associated with occlusive vascular disease needs further investigation.
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PMID:Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro. 243 57

Aspirin inhibits thromboxane and prostaglandin formation in platelets and in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in arachidonic acid metabolism. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long-term aspirin treatment for the secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. The combination of aspirin and streptokinase was significantly better than either drug alone. On the other hand, two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for the prevention of vascular disease.
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PMID:Aspirin, platelets and prevention of vascular disease. 251 99

Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and beta-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of alpha 1- and beta 1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.
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PMID:Platelet activation and secretion associated with emotional stress. 298 76

We have studied the effect of indobufen, a cyclo-oxygenase blocking agent which has proved useful in patients with obstructive vascular disease, on red blood cell (RBC) filterability in vitro and in a pilot study ex vivo. The addition of indobufen in vitro to blood samples from 10 healthy volunteers did not significantly modify RBC deformability. We evaluated the ex vivo effect of indobufen (200 mg bd) in 14 patients with obstructive vascular disease. A significant improvement in RBC deformability was noted on the 5th, 14th, and 28th days of treatment, 2 h after the morning dose. Acetylsalicylic acid given to 6 similar patients had no effect suggesting that the positive haemorheological effect of indobufen is probably not linked to its cyclooxygenase blocking effect.
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PMID:In vitro and ex vivo effects of indobufen on red blood cell deformability. 358 87

Accumulating experimental and clinical evidence indicates that a time for reappraisal of therapeutic modalities designed to inhibit the eicosanoid pathway as it may affect vascular disease may be approaching. Pharmacologic agents originally used were chosen because they were capable of suppressing platelet functions such as aggregation, release, and adhesion. The goals of clinical trials were to evaluate medications that would prevent or reduce platelet accumulation in critically located blood vessels of the heart, brain, and extremities and on vascular prostheses. Evaluation of results of therapeutic trials has been difficult and this is superimposed on less-than-complete knowledge of the basic pharmacology of the drugs that have been used. Participation of neutrophils and possibly macrophages in the thrombotic process is now well recognized on morphologic grounds. Because different cell types such as platelets, neutrophils, and endothelial cells have been shown to interact biochemically by sharing precursors and intermediates of the eicosanoid pathway, the pharmacologic approach to inhibition of vascular disease may require reevaluation. Neutrophils appear to lack a cyclooxygenase pathway but serve as a source of the lipoxygenase product leukotriene B4 (LTB4). Actions of LTB4 include neutrophil aggregation, adhesion of neutrophils to endothelial cells, chemotaxis, chemokinesis, and plasma exudation. We have demonstrated in vitro that released free arachidonic acid from aspirin-treated platelets can serve as a source of neutrophil LTB4. Leukotrienes C4, D4, and E4 are agonists for various functions of vascular endothelium and smooth muscle. Most pharmacologic agents used in the treatment of vascular diseases inhibit the cyclooxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of platelet function in thrombosis. 389 60

Diabetes is characterized by hyperglycemia, a relative lack of insulin, and an inclination to vascular disease and neuropathy. The link between diabetes and vascular disease is not understood, but autonomic dysfunction could partly account for alterations in reactivity of diabetic blood vessels to neurotransmitters and circulating hormones. Changes in local control of vascular tone, such as imbalance in production of relaxing and contracting factors by the endothelium, may be related to the initiation and maintenance of abnormal vascular reactivity characteristically seen in diabetic vascular complications. The emphasis is to discuss functional changes of blood vessel adrenergic neuroeffector mechanisms and endothelial cell dysfunction, together with the complex interrelationship of cyclooxygenase catalysis, protein kinase C activity, sodium-potassium ATPase activity, and flux through the polyol pathway. This review focuses on the common mechanisms by which hyperglycemia causes changes in vascular function.
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PMID:Diabetes and vascular disease: functional alterations in adrenergic neurotransmission and endothelium. 774 65

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and joint erosions. It affects approximately 1% of the adult population in a female/male ratio ranging from 2:1 to 4:1. RA is an insidious disease, typically having an onset of symmetric joint swelling and reaching a peak incidence in the fourth and fifth decades. Extraarticular manifestations include pulmonary, ocular, and vascular disease. The etiology of RA remains unknown. Attempts to discover infectious causes have proven unsuccessful, although environmental influences may trigger a response leading to the development of this autoimmune disease. Genetic associations have been identified, particularly with the major histocompatibility complex class II antigens. Furthermore, twin studies have shown a 30%-50% concordance rate for monozygotic twins. Approximately 70%-80% of patients with RA have rheumatoid factor present in the blood, although its role remains unclear. Hormonal status may influence RA. The majority of RA patients are women, and in 75% of them, the disease improves during pregnancy. RA has significant financial and social implications associated with treatment costs, lost wages, disability, and increased mortality. Mainstays of medical therapy have included nonsteroidal anti-inflammatory and immunosuppressive agents, such as prednisone and methotrexate. Recent advances in the treatment of RA include specific inhibitors of cyclooxygenase II, T cells, blood vessels, cytokines (such as tumor necrosis factor-alpha [TNF-alpha] or interleukin-1 [IL-1]), and adhesion molecules. Additional studies are ongoing with combination interventions. It is anticipated that a better understanding of the basic pathophysiologic mechanisms critical in RA pathogenesis will provide more precise and efficacious therapy.
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PMID:Rheumatoid arthritis: current clinical and research directions. 943 37


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