Platelet inhibition by endothelium‐derived relaxing factor from the rabbit perfused aorta

• Published in: British journal of pharmacology 1988-12, Vol.95 (4), p.1308-1314
• Main Authors: Bult, Hidde, Fret, Hermine R.L., Bossche, Rita M., Herman, Arnold G.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Biological and medical sciences; Biological Factors - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; endothelium-derived relaxing factor; Epoprostenol - metabolism; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Indomethacin - pharmacology; Nitric Oxide; Perfusion; Platelet Aggregation - drug effects; platelets; Rabbits; Vertebrates: blood, hematopoietic organs, reticuloendothelial system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb11769.x

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 F1α. 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 indo‐methacin. 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.