[The role of guanyl cyclase in the regulation of aggregation of human thrombocytes]

Abstract

Increased platelet aggregability is one of the etiological factors of vascular diseases. It is suggested that the cGMP system is involved in the negative regulation of platelet aggregation. The study of platelet guanylate cyclase (GC), a key enzyme of the cGMP system, permits a more thorough understanding of biochemical control of aggregation and opens a possibility of the development of specific action on platelets in pathological states of hemostasis. The authors have revealed a high linear correlation between the increase in aggregability and the decrease in GC activity and in its response to the NO-containing compound sodium nitroprusside (SNP). During ADP-induced aggregation, the state of GC activation by SNP increases (due to saturation of the enzyme by endogenous heme); the platelet cGMP content also rises. In platelets with prevented aggregation (SNP before ADP), GC parameters remain unchanged. NP caused disaggregation of irreversibly aggregated platelets and accelerated disaggregation in the case of reversible aggregation. NO is known to be an endogenous activator of GC and this circumstance gives an opportunity of direct action on platelets (with the help of NO-containing drugs) in order to diminish their hyperaggregability and to prevent spontaneous aggregation that takes place in vascular diseases.