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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anesthesized male rabbits having a resting mean arterial pressure of 81 +/- 4 mm Hg and superior mesenteric artery blood flow of 91 +/- 7 mL min-1 were subjected to 60 min of splanchnic ischemia followed by 60 min of reperfusion. Upon reperfusion, mean arterial pressure fell. Splanchnic blood flow also decreased but not in parallel with blood pressure; consequently, vascular resistance was increased over the reperfusion period. This increase in splanchnic vascular resistance was not affected by intravenous t-PA (0.5 mg kg-1 + 5 mg kg-1 hr-1) for 30 min prior to and throughout the reperfusion period or by intravenous L-NAME (1 mg kg-1 x 2). However, intravenous infusions of TGF-beta (18 or 54 micrograms kg-1) at the time of reperfusion dose dependently attenuated the increases in vascular resistance (p < 0.05). This effect of TGF-beta was enhanced by coadministration of t-PA and inhibited by the coadministration of L-NAME. We propose that the effects of TGF-beta are ultimately mediated via nitric oxide release, and conclude that this may be useful therapy for the prevention of reperfusion-associated injury following surgery or as an adjunct to thrombolytic therapy.
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PMID:Transforming growth factor-beta 1 inhibits postischemic increases in splanchnic vascular resistance. 130 30

In patients with coronary heart disease platelet activity may be pathologically increased. Administration of platelet inhibitor drugs is an established treatment principle. The interactions between platelet activation, platelet inhibitor drugs like acetylsalicylic acid (ASA) or molsidomine and the endogenous fibrinolysis were studied in three trials. Platelet aggregation and thromboxane synthesis are dose- dependently inhibited after oral intake of ASA (0, 10, 30, 100 or 500 mg/d) Additional intake of the antianginal agent and nitric oxide donator Molsidomine (8 mg) results in a synergistic platelet inhibitor effect characterized by a significantly delayed aggregation response. In a group of patients with coronary artery stenoses platelet activity was markedly enhanced, when compared to healthy individuals. During physical exercise platelet activity was even further enhanced and plasma t-PA-activity was increased by a factor of 2.2. The stimulation of the endogenous fibrinolytic system was markedly reduced when compared to healthy subjects. Following successful coronary angioplasty 393 patients were randomized to receive either molsidomine (2 x 8 mg/d) or ASA (1 x 500 mg/d) plus nifedipine (3 x 20 mg/d). Coronary angiography performed after the 6 month treatment period revealed a restenosis rate of 29% in the molsidomine group and of 33% in patients treated with ASA + nifedipine. This difference was not statistically significant.
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PMID:[Modification of thrombocyte function in diagnostic and therapeutic interventions in cardiology]. 177 38

The vascular endothelium, which envelopes the circulating blood in a continuous monolayer, is not only a physical barrier between blood and vessel wall, but a highly complex "organ" which is involved in the regulation of blood vessel tone and permeability, blood coagulation, angiogenesis, leukocyte and platelet reactivity, phagocytosis of bacteria and the metabolism of many vascular mediators. This article focuses on the biosynthesis, biological actions and interactions of endothelium-derived vasoactive mediators, namely, prostacyclin, endothelium-derived relaxing factor--now characterized as nitric oxide--and endothelin, in the regulation of blood vessel tone under physiological and pathophysiological conditions. The formation of these highly vasoactive substances in modulated by changes in intracellular messengers (cyclic adenosine monophosphate, cyclic guanosine monophosphate, calcium), by interactions of endothelium with blood-borne cells and plasma constituents and finally by the interaction of these mediators themselves. The current evidence supports the view that nitric oxide plays a pivotal role for the regulation of blood vessel tone under physiological conditions, while the generation of prostacyclin is primarily an important defense mechanism to maintain a sufficient blood vessel patency and tissue viability under conditions of a compromised blood supply. Although the physiological role of the endothelium-derived vasoconstrictor peptide endothelin-1 is less well defined, it is apparent that any potential harmful vasoconstrictor effects resulting from an enhanced formation of endothelin under pathophysiological conditions are modulated by the simultaneous generation of prostacyclin, nitric oxide and tissue-plasminogen activator, thus preventing excessive vasoconstriction and thrombotic occlusion of the vascular bed concerned.
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PMID:Biosynthesis and interaction of endothelium-derived vasoactive mediators. 178 95

Since L-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects of L-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynaud's phenomenon. After therapy, patients with Raynaud's phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.
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PMID:L-arginine therapy in Raynaud's phenomenon? 181 64

Endothelial cells produce at least three substances that can attenuate the platelet aggregation response: tissue-type plasminogen activator; the platelet inhibitory prostaglandins I2 and E1; and endothelium-derived relaxing factor, one form of which exhibits properties of nitric oxide. Since platelet aggregates formed in vivo are involved in the initiation of many clinically important occlusive vascular syndromes, we tested the hypothesis that these endothelial products act synergistically to disperse platelet aggregates. Our data reveal that tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin (an organic nitrate activator of guanylate cyclase analogous to endothelium-derived relaxing factor) act synergistically to disaggregate platelets and do so in part by modulation of platelet cyclic nucleotides. These data suggest a potential mechanism by which the endothelium protects against the formation of platelet aggregates in vivo and offer a potential strategy for improving the efficacy of thrombolytic therapy.
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PMID:Synergistic disaggregation of platelets by tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin. 250 9

Among endothelial secretogogues prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B2 kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI2 is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI2, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI2 analogues, whereas exogenous PGI2 or TXA2 synthase inhibitors (i.e. following increase in endogenous PGI2) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI2, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.
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PMID:Interactions between endothelial secretogogues. 754 32

Endothelial cells are responsible for the secretion or surface expression of a wide variety of mediators involved in the control of thrombosis. These include von Willebrand factor, prostacyclin, nitric oxide, thrombomodulin, tissue-type plasminogen activator and its inhibitor, tissue factor and the tissue factor pathway inhibitor. The production of each of these can be modulated; in some cases very rapidly in response to external stimuli, in other cases more slowly. Thrombin is a key stimulus, which affects the production of almost all of these mediators. In addition, several cytokines and bacterial endotoxins shift the balance of endothelial mediator secretion from the basal anticoagulant profile towards a procoagulant profile.
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PMID:Vessel wall interactions regulating thrombosis. 780 30

Healthy endothelium is a metabolically active interface between the blood and extravascular tissues. Its intimal surface is anticoagulant and antithrombotic, and it secretes a variety of molecules involved in regulating platelet function and blood coagulation. The rapid interactions between platelets, their secreted components, or thrombin and endothelial cells at sites of vessel damage ensure the local secretion of mediators such as prostacyclin and nitric oxide that limit the intravascular growth of the haemostatic plug. There is considerable evidence that a decreased ability of endothelial cells to synthesize NO contributes to the pathogenesis of arterial disease. Local deficiency of PGI2 synthesis has also been implicated in the thrombotic problems in haemolytic uraemic syndrome. Endothelium is also the source of circulating von Willebrand factor, important for efficient platelet adhesion. Chronically elevated plasma levels of vWF in a series of diseases where there is vascular pathology apparently reflect endothelial cell damage or activation, and may contribute to the prothrombotic tendency they exhibit. They may be compounded by decreased levels of the surface anticoagulant thrombomodulin, if the increased concentrations of the soluble forms of thrombomodulin detected in the circulation under similar conditions are a reflection of loss from the endothelium. Further alterations of function in a procoagulant/prothrombotic direction take place when endothelial cells are exposed to certain cytokines or lipopolysaccharide. Tissue factor synthesis is induced, thrombomodulin expression is decreased, and there is enhanced sensitivity of vWF secretion. In addition, the balance of tissue-type plasminogen activator and plasminogen activator inhibitor type I secretion is changed in favour of the latter. These processes are each likely to contribute to the occurrence of disseminated intravascular coagulation which can accompany septic shock.
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PMID:Endothelial cell function and thrombosis. 784 94

Endothelial cell products contribute to many aspects of the regulation of haemostasis. They include potent inhibitors of platelet aggregation (prostacyclin and nitric oxide) rapidly released in response to agonists such as thrombin. Similar agonists also induce the formation of platelet-activating factor by endothelium. Endothelial cell surface ectonucleotidase enzymes control the catabolism of platelet-active adenine nucleotides. The main source of the circulating coagulant cofactor von Willebrand factor is the endothelium, where it is stored in granules for agonist-triggered exocytosis and also secreted constitutively. Surface anticoagulant activities are due to the presence of antithrombin and thrombomodulin. Endothelial cells also secrete plasminogen activator and its inhibitor. Many of these reactions are significantly modulated by exposure of endothelium to cytokines or bacterial endotoxin, the most striking example being the new synthesis and surface expression of the procoagulant tissue factor (thromboplastin).
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PMID:The control of production and release of haemostatic factors in the endothelial cell. 802 46

The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 microM) were used to induce release of t-PA and vWF. The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP. The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP. None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.
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PMID:The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor. 809 63


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