Vaso-contractile responsiveness of perfused arterial segments to platelet-derived thromboxane A2.
It remains not entirely accepted that changes in prostanoid metabolism in the blood vessel wall, as well as in whole blood, have a certain influence on vascular responsiveness to vasoactive agents. The aim of the present study is to elucidate whether platelet-derived thromboxane A2 (TxA2) participates in enhancement of vasoconstractile response to a pressor agent. Platelet aggregation was extraluminally induced by application of collagen to autologous platelet rich plasma (PRP), and then the PRP treated with collagen was infused into the perfusion system by means of a small infusion pump. All the prostanoids in the perfusate were assayed radioimmunologically. Infusion into the perfusion system of PRP treated with collagen, as well as that of untreated PRP, apparently caused pronounced enhancement of vasocontractile response to noradrenaline (NA), accompanied by elevations of both the level of TxB2, a stable metabolite of TxA2, and the TxB2/prostaglandin E (PGE) ratio. In addition, treatment with either OKY-046 (a Tx A2 synthetase inhibitor) or ketanserin (a selective S2-serotonergic antagonist) resulted in diminution of the raised vasoconstrictor response to NA induced by application of collagen to PRP. Thus, it is possible to draw the conclusion that platelet-derived TxA2, is as potent a vasoactive substance as 5-hydroxytryptamine (5-HT) and at least in part, contributes to the enhancement of vasocontractile response to NA (NA-R) during raised platelet aggregability.
Michibayashi
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Central Clinical Laboratory, Sapporo Medical College, Japan.
D000818:Animals; D001158:Arteries / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D008689:Methacrylates; D013928:Thromboxane A2; D003094:Collagen; C034364:ozagrel; D009638:Norepinephrine