Platelet inhibition by endothelium-derived relaxing factor from the rabbit perfused aorta.
1. The platelet inhibiting activity of endothelium-derived relaxing factor (EDRF) released by the perfused thoracic aorta of the rabbit was investigated. 2. The aortic effluent superfused a ring of the abdominal aorta without endothelium in order to bioassay EDRF. Aliquots of effluent were collected on rabbit washed platelets and aggregation induced by U-46619 was measured after 1 min. Prostacyclin (PGI2) was monitored by radioimmunoassay of 6-oxo-prostaglandin F1 alpha. 3. Acetylcholine (ACh) caused a dose-dependent secretion of EDRF, PGI2 and anti-aggregating activity. Plasma and methylene blue suppressed the platelet inhibition by the effluent. 4. The PGI2 content of the effluent was not sufficient to account for all the anti-aggregating activity. However, the platelet inhibition disappeared when PGI2 formation was blocked with indomethacin. 5. Compression of the thoracic aorta increased the EDRF content in the effluent. A transient secretion of anti-aggregating activity was then observed in aortic effluent in the absence of PGI2. This activity coincided with the presumed EDRF peak in the effluent. 6. Superoxide dismutase enhanced the ACh-induced EDRF content and revealed secretion of an anti-aggregating substance when PGI2 formation was blocked. Pretreatment of the platelets with subthreshold concentrations of PGI2, or the cyclic GMP phosphodiesterase inhibitor RX-RE 56, also revealed the release of a labile platelet inhibitor in response to ACh. 7. The results indicate that EDRF released by fresh aortic endothelium may suppress platelet aggregation, particularly when PGI2 is present.
Bult
H
H
University of Antwerp (UIA), Division of Pharmacology, Wilrijk, Belgium.
Fret
H R
HR
Van den Bossche
R M
RM
Herman
A G
AG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001685:Biological Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits
D001685:Biological Factors; D009569:Nitric Oxide; D011464:Epoprostenol; D000109:Acetylcholine; D007213:Indomethacin