Altered platelet reactivity

In this chapter, literature dealing with altered platelet function in hypertension will be reviewed to develop a better imderstanding of the role of agonist-receptor mediated signal transduction and Ae ensuing biochemical reactions that may be responsible for altered platelet reactivity in hypertension. 

Perry BD, GiUer EL, Southwick SM (1987) Altered platelet alpha2 adrenergic binding sites in posttraumatic stress disorder. Am J Psychiatry 144 1511-1512 Przbyslawski J, Sara SJ (1997) Reconsolidation of memory after its reactivation. Behav Brain... 

Ifthe expression of G responsible for stimulation of adcnylyl cyclase, is the same in the platelets from normotensive and hypertensive humans and animals then the increased platelet reactivity to PGE, in hypertension may be due to differences in the G protein associated GTPase activity. We have examined this possibility and shown that PGE, induces a greater stimulation of GTPase activity in platelet membranes from SHR (806%) than from WKY (46%) platelets (Fig. 8). These data clearly suggest that increased platelet reactivity to PGE, and possibly thrombin, in hypertension may be due to altered signal transduction. 

When each of the acrylate or methacrylate polymers was preincubated with whole plasma, the platelet reactivity of the surfaces upon subsequent exposure to whole blood decreased significantly (Fig. 3). On the other hand, with many other polymers this effect of plasma was not seen. Of 20 varieties of segmented polyurethanes examined, none showed this behavior (22), and platelet adhesion to polystyrene was also unaffected by plasma pretreatment ( ). The phenomenon of plasma-induced passivation of methacrylate and acrylate polymers presumably involves selective adsorption of specific plasma proteins by the surfaces and/or a particular alteration of the adsorbed protein once bound. 

Chitosan is the main structural component of crab and shrimp shells. Chitosan contains both reactive amino and hydroxyl groups, which can be used to chemically alter its properties under mild reaction conditions. Al-acyl chitosans were already reported as blood-compatible materials. UV irradiation grafting technique was utilized to introduce obutyrylchitosan (OBCS) onto the grafted SR film in the presence of the photosensitive heterobifunctional cross-linking agent. The platelet adhesion test revealed that films grafted on OBCS show excellent antiplatelet adhesion. 

Lipoxygenase metabolites of arachidonic acid such as 12-hydroxyeicosa-tetraenoic acid (12-HETE) have been shown to be involved in the release of neurotiansmitters and other cellular functions (92-94). Basal generation of 12-HETE has been reported to be about 3.7-fold greater in SHR than in WKY platelets (95,96). Arachidonic acid has been shown to stimulate platelets by activating protein kinase C, by a prostaglandin-independent mechanism (97). It is possible that the lipoxygenase metabolites of arachidonic acid may also be involved in altered reactivity in hypertension. 

The work discussed here has shown that suspensions of platelets and red cells in a physiological medium can provide information for platelet surface interactions. Evidence is provided on the dynamic features of platelet-surface adhesion and detachment which indicates that more than one sequence of adhesion, detachment and re-adhesion can lead to the same net platelet adhesion. Surface generated substances, such as A DP and serotonin from platelets and thrombin from the coagulation pathway, may strongly influence the function of platelets approaching a surface. The supply of these substances depends on the presence of flow and continued arrival of platelets at a surface. The reactivity of surface-bound protein may be altered by platelet adhesion and detachment. This may occur as a result of deposition of cell membrane components, replacement of the original substrate with protein secreted from platelets or possibly by enzymatic digestion of surface bound protein. 

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