Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit.
The effects of porcine endothelin (endothelin-1, ET-1; 1 nmol/kg i.a.) on ex vivo platelet aggregation and platelet cAMP/cGMP levels were investigated in the anesthetized rabbit. ET-1 inhibited ADP-induced platelet aggregation by 83 +/- 9% within 5 min (p less than 0.01). This ET-1-induced inhibition of platelet aggregation lasted for 30 min and was associated with a significant (five- to sixfold) increase in platelet cAMP. However, platelet cGMP levels were unaffected. Indomethacin (5 mg/kg i.v., 20 min prior to ET-1) abolished the ET-1-induced inhibition of ex vivo platelet aggregation as well as the corresponding augmentation of platelet cAMP. Thus, ET-1 inhibits platelet function in vivo due to the release into the circulation of antiplatelet cyclo-oxygenase products, such as prostacyclin (or PGD2).
Thiemermann
C
C
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England.
Lidbury
P S
PS
Thomas
G R
GR
Vane
J R
JR
D000758:Anesthesia; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D011817:Rabbits
D016232:Endothelins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D007213:Indomethacin