Platelet aggregation and vasoconstriction related to platelet cyclooxygenase and 12-lipoxygenase pathways.
Many thrombotic angiopathies originate as a result of an abnormal interaction between platelets and blood vessel walls. The present study focused on the platelet activating factor (PAF)-induced platelet aggregation mechanism and was undertaken to clarify the association between platelet aggregation and vasocontractility. Vasoconstriction was examined in perfused artery segments dissected from the central ear artery of male rabbits. Autologous platelet rich plasma (PRP) was infused into the perfusion system. Vasocontractility was examined in response to PRP plus PAF or collagen. The vasocontractile response to noradrenaline (NA-R) on perfusion of PRP plus PAF was initially augmented, then gradually attenuated. The platelet aggregation in response to PAF was constant and longlasting and moderately inhibited by nordihydroguaiaretic acid, a 12-lipoxygenase (LOX) inhibitor, but was unaffected by indomethacin, a cyclooxygenase inhibitor. The attenuated responses disappeared and NA-R was returned to the initial level on pretreatment with tetrodotoxin which excluded neurogenic components from the arterial preparation. In contrast, a repetitive NA-R to PRP plus collagen gradually increased. Thus, it may be concluded that PAF-induced platelet aggregation participates in activation of the 12-LOX pathway and is accompanied by the release of vasodepressor nerve-stimulating substances from platelets.
Michibayashi
Tsutomu
T
Clinical Pathophysiology, Division of Human Comprehensive Medicine, Graduate School of Medicine, Sapporo Medical University, Sapporo, Japan. michibay@sapmed.ac.jp
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology*; D003094:Collagen / Q000502:physiology*; D004423:Ear / Q000098:blood supply; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011453:Prostaglandins / Q000097:blood; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013929:Thromboxane B2 / Q000097:blood; D046509:Tissue Culture Techniques; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D010972:Platelet Activating Factor; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013929:Thromboxane B2; D003094:Collagen; D001092:Arachidonate 12-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine