Potentiation with epinephrine of macaque platelet aggregation by other agonists: Implications for studies on human atherosclerosis

Beatty, Clarissa H.; Howard, Charles F.; Caruso, Valerie

doi:10.1016/0049-3848(86)91690-7

Cited by 12 publications

(8 citation statements)

References 15 publications

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“…Epinephrine exerts additional sheardependent and -independent actions on platelet aggregation. 14 The antithrombotic efficacy of local TFPI gene transfer in the presence of heightened shear stress is not unexpected. Indeed, among all platelet agonists known, thrombin is the most potent, and systemic administration of the direct antithrombin hirudin has been effective in preventing plateletrich thrombus formation in pigs, in other animal species, and in the course of acute coronary syndromes in patients.…”

Section: Discussionmentioning

confidence: 99%

“…If the pigs did not develop CFVs after 70% constriction, epinephrine was infused to increase local shear stress and platelet activation. 14 Epinephrine was administered at doubling rates from 1.5 to 38 g/min (10 minutes per dose). In the absence of irreversible zero flow, the infusion was continued for a total of 30 minutes at 38 g/min before the pig was killed.…”

Section: Assessment Of Antithrombotic Effects Of Local Tfpi Gene Tranmentioning

confidence: 99%

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Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

et al. 2000

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Background-Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of factor Xa and the coagulant initiator complex tissue factor/factor VIIa. Methods and Results-To study the effects of TFPI gene transfer on thrombus formation, balloon-injured porcine carotid arteries were treated locally with an adenovirus encoding human TFPI (Ad-TFPI) or control virus. Gene transfer of TFPI was confirmed by detection of human TFPI in the conditioned medium of porcine carotid arteries kept in culture after in vivo transduction. When carotid flow was measured with Doppler probe 5 days after surgery, cyclic flow variations (CFVs) developed in 7 of 8 control pigs after constriction of the injured carotid artery by 40%, and all control-treated arteries occluded after 70% constriction. In contrast, CFVs were observed in only 1 of 8 Ad-TFPI-treated pigs after 40% constriction, and only 3 of 8 occluded after constriction by 70% (Pϭ0.0027 and Pϭ0.007, respectively).

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Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Antithrombotic Effects Of Local Tfpi Gene Tranmentioning

confidence: 99%

Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

et al. 2000

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“…In primates other than humans and in most mammalian species catecholamines exert potentiating effects on platelet response to other agonists, but are unable to induce aggregation even in citrated PRP samples [192,193].…”

Section: In Vitro Catecholamine Effectsmentioning

confidence: 99%

Role of catecholamines in platelet function: pathophysiological and clinical significance

Anfossi

Trovati

1996

Eur J Clin Investigation

167

107

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Platelets are involved in the pathogenesis of vascular damage in both atherosclerosis and arterial hypertension. Their reactivity in vivo is influenced by different factors, including sympathoadrenal activation, plasma levels of atherogenic lipoproteins and haemorrheological changes. In the present review, we examine the modulation of platelet function by the sympathoadrenal system and concentrate on the role of circulating catecholamines in the control of platelet responses. Human platelets exhibit both adrenergic and dopaminergic receptors that are influenced by different catecholamines. alpha(2)-Adrenoceptors of alpha(2A) subtype prevail on platelet membrane; through their stimulation, catecholamines potentiate the effects of other agonists and, at higher concentrations, initiate platelet responses, including aggregation, secretion and arachidonate pathway activation. Physiological and pathological conditions causing sympathoadrenal activation in vivo, i.e. physical activity, mental stress, insulin-induced hypoglycaemia, acute coronary ischaemia and heart failure, modify the circulating platelet populations and modulate platelet reactivity through an increase in circulating catecholamines. A sympathoadrenal hyperactivation modifies the function of circulating platelets through direct catecholamine effects, catecholamine-induced changes of haemodynamic factors and lipid pattern and inhibition of the vascular eicosanoid synthesis. The catecholamine effects on platelet function can be involved in the interplay among stress, adrenomedullary system activation and cardiovascular diseases.

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“…In control experiments, pervanadate alone up to 1 m m had little effect on rat platelet aggregation (data not shown). Epinephrine, acting on platelet α 2A ‐adrenoceptors, does not initiate activation of rat platelets by itself, but rather potentiates the responses to other agonists, such as ADP [21]. In this regard, epinephrine increased TSSP‐induced platelet aggregation in a concentration‐dependent way, which could be reversed by the α 2 ‐antagonist phentolamine (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pennogenin glycosides with a spirostanol structure are strong platelet agonists: structural requirement for activity and mode of platelet agonist synergism

Fu¹,

Yu²,

Tang³

et al. 2008

Journal of Thrombosis and Haemostasis

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Summary. Background: Steroidal saponins have long attracted scientific attention, due to their structural diversity and significant biological activities. For example, total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs) constitute an effective treatment for abnormal uterine bleeding. Objective: To determine the active constituents in TSSPs and elucidate the mechanisms that underlie their in vivo pharmacologic actions on hemostasis. Methods: Steroidal saponins were purified by chromatography, and their effects upon hemostasis and platelet function were evaluated by tail bleeding time in mice and rats, aggregometry, flow cytometry and Western blotting. Results: TSSPs promoted hemostasis in vivo and dose-dependently induced rat or human platelet aggregation in vitro. Using bioassay-guided separation, four known pennogenin glycosides with a spirostanol structure were identified as the active ingredients of TSSPs. A structure-activity assay showed that the aglycone and sugar moieties of pennogenin glycosides are both essential for their aggregatory activity. Their synergistic actions on platelet aggregation were observed with pennogenin glycosides and with other known platelet agonists, suggesting that these glycosides are platelet agonists. Aggregation in response to the pennogenin glycosides involved a IIb b 3 activation, was inhibited by cAMP, was dependent upon extracellular calcium, secreted ADP and thromboxane synthesis, and was mediated by phosphatidylinositol-3-kinase. Conclusion: We identified pennogenin glycosides with a spirostanol structure as the active ingredients of Paris polyphylla Sm. var. yunnanensis in promoting hemostasis in vivo. Their mode of their action on platelets suggests that they represent a new type of platelet agonist.

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Potentiation with epinephrine of macaque platelet aggregation by other agonists: Implications for studies on human atherosclerosis

Cited by 12 publications

References 15 publications

Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor

Role of catecholamines in platelet function: pathophysiological and clinical significance

Pennogenin glycosides with a spirostanol structure are strong platelet agonists: structural requirement for activity and mode of platelet agonist synergism

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