Inhibition of platelet aggregation with histamine

Mazza, Joseph J.; Gatlin, Patience F.; Marx, James J.

doi:10.1002/ajh.2830080303

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…38,39 When the mesentery of a C57BL/6 mouse was suffused with 50 L histamine (10 g/mL) there was a prompt stoppage of flow of normal blood in the microvasculature detected using FITC-labeled blood flow (data not shown), as had been observed with PAR-1 agonist peptide. This is consistent with histamine-induced expression of P-selectin on endothelial cell surfaces 40 causing flow stoppage.…”

Section: Microvascular Flow Velocity Changes In Mice Following Activamentioning

confidence: 69%

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Embury

Matsui²,

Ramanujam³

et al. 2004

Blood

126

121

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Microvascular occlusion in sickle cell disease can be initiated by adhesion of sickle red blood cells (RBCs) to the endothelium. Our objective in this study was to verify the relevance in vivo of our discovery that sickle RBCs adhere abnormally to endothelial P-selectin in vitro. We used computer-assisted intravital microscopy to characterize RBC flow velocity (V RBC ) in mice. We found faster V RBC of sickle RBCs in P-selectin knock-out and control mice than in sickle cell mice, which have increased endothelial cell P-selectin expression. Agonist peptide for murine protease-activated receptor-1 (PAR-1), which selectively activates mouse endothelial cells but not platelets, was used to assess the effects of endothelial cell Pselectin on microvascular flow. Suffusion of venules with this agonist stopped flow promptly in normal and sickle mice but not in P-selectin knock-out mice or in control mice pretreated with anti-P-selectin monoclonal antibody or unfractionated heparin (UFH). Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, provided flow had not already stopped. We conclude that endothelial cell P-selectin contributes to the microcirculatory abnormalities in sickle cell disease and that blocking Pselectin may be useful for preventing painful vasoocclusion in sickle cell disease. ( IntroductionMost of the morbid consequences of sickle cell disease are caused by the impairment of blood flow in the microvasculature. 1 Traditional understandings attribute the microvascular occlusion to an increase in blood viscosity caused by intraerythrocytic polymerization of deoxygenated sickle hemoglobin and the consequent sickling and rigidification of red blood cells (RBCs). 2 Kinetic considerations predict that, in the absence of preexisting intraerythrocytic polymer, impairment of blood viscosity will occur after the RBC has entered into veins too large to be occluded by rigid sickled RBCs 3 and that polymerization will occur within vessels small enough to be occluded by individual sickled RBCs only when their transit through the microcirculation is delayed.Among the factors that can prolong the transit time of sickle RBCs through the microvasculature are several polymerizationindependent processes, including vascular constriction, coagulation, inflammation, and cellular adhesion. 4 Experimental evidence supports a 2-step mechanism of vasoocclusion initiated by the binding of an adhesive subset of sickle RBCs to the vascular endothelium and completed by the logjamming of more rigid sickle RBCs behind the adherent nidus. 5 This discovery has provided an understanding of the onset of painful vasoocclusion that is lacking from detailed explications of hemoglobin S polymerization and RBC sickling and notions of systemic deoxygenation 6 and inspired a profusion of research into mechanisms of adhesion and adhesion-blocking therapies. 7,8 The expression of cytoadhesion molecules on endothelial cells isolated from the circulating blood of patients with sickle cell disease 9 and on intact endothelial c...

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Section: Microvascular Flow Velocity Changes In Mice Following Activamentioning

confidence: 69%

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Embury

Matsui²,

Ramanujam³

et al. 2004

Blood

126

121

View full text Add to dashboard Cite

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“…The effect of histamine on platelet functions has been studied in a few reports. Thus histamine will increase cyclic AMP levels in human platelets, probably via H2 receptors (6), whereas histamine inhibits platelet aggregation and thrombin-induced serotonin release (7,8). In the study by Norn et a1 (8), evidence was forwarded that the effect was mediated via H2 as well as HI receptors.…”

Section: Discussionmentioning

confidence: 99%

Demonstration of Histamine Receptors on Human Platelets by Flow Cytometry

Hallberg

Dohlsten

Baldetorp

1984

Scandinavian Journal of Haematology

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Fluoresceinated human albumin conjugated with histamine (FHA‐HIS) has been used for the demonstration of histamine receptors on human platelets. Such receptors were demonstrated on 40–63% of peripheral blood platelets in 4 healthy donors. The binding of FHA‐HIS was inhibited on 35–79% of the platelets by the histamine H1 receptor antagonists diphenhydramine and clemastine. The histamine H2 receptor antagonist cimetidine blocked the FHA‐HIS binding on 14–37% of the platelets. It is concluded that histamine H1 as well as H2 receptors occur on human platelets but the receptors are not equally distributed in the platelet population.

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Inhibition of platelet aggregation with histamine

Cited by 2 publications

References 18 publications

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo

Demonstration of Histamine Receptors on Human Platelets by Flow Cytometry

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