Rat's vessel wall generates an antiaggregatory substance independent of prostacyclin production.
We have investigated whether the vessel wall may release or synthetize some substance able to modify the platelet function independent of prostacyclin (PGI2) production. Twenty female rats were injected with indomethacin. 18 hours after the injection animals were sacrificed and rings cut from thoracic and abdominal aorta were obtained. They were incubated in Krebs solution for different periods of time after which an aliquot from the indomethacin treated rat's aortic ring (ITRAR) was assayed on platelet aggregation induced by several agonists. The supernatant from the 40 min. incubation mixture of ITRAR released a substance which completely inhibits platelet aggregation induced by arachidonic acid (AA), ADP, epinephrine, collagen, ristocetin and thrombin. The time of appearance of the substance varied with a mean of 17 min.. It is released with and without AA stimulation. Once generated it is active for at least three hours; its antiaggregating activity remains even if it is boiled for 15 sec, incubated at 37 degrees C, or if the vessel is treated with tranylcypromine. Platelet aggregation inhibition is still evident if the supernatant from ITRAR is transferred to a platelet rich plasma (PRP) from a normal donor who had taken an aspirin 24 hours before sampling. All these results indicate that this substance released from ITRAR is not prostacyclin. Nordihydroguaiaretic or eicosatetraynoic acid which are lipoxygenase inhibitors could not modify the ITRAR's release; nor did mepacrine which is a phospholipase inhibitor. Since mepacrine does not completely inhibit phospholipase activities we cannot exclude the possibility that the substance is derived from AA. More studies are in progress to elucidate the biochemical properties of this substance.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats
D002396:Catechols; D015117:5,8,11,14-Eicosatetraynoic Acid; D009637:Masoprocol; D001241:Aspirin; D007213:Indomethacin