Endothelins release tissue plasminogen activator and prostanoids.
Endothelin (ET)-1 (0.1-1 nmol/kg), ET-2 (0.1-1 nmol/kg) or ET-3 (0.3-3 nmol/kg) dose dependently inhibited platelet aggregation induced by adenosine di-phosphate (ADP) ex vivo in anaesthetised rabbits, while having no effect on aggregations induced by ADP, collagen or arachidonic acid in vitro. This anti-aggregatory effect of the peptides is most likely due to the release of prostacyclin into the circulation, for the inhibition was abolished by an injection of indomethacin (5 mg/ml). All three peptides produced a significant, bi-phasic reduction of the euglobulin clot lysis time. This ET-induced enhancement of plasma fibrinolytic activity was associated with a release of tissue plasminogen activator into the circulation. ET-1 or ET-2 caused a transient decrease in left ventricular systolic pressure (LVSP) followed by a prolonged pressor response. However, ET-3, while inducing a similar transient fall in LVSP caused a second, more prolonged, decrease in LVSP. The haemodynamic responses to all three peptides were modulated by the release of prostanoids, as evidenced by the elevation of the pressure responses by indomethacin.
Lidbury
P S
PS
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, U.K.
Thiemermann
C
C
Korbut
R
R
Vane
J R
JR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005343:Fibrinolytic Agents; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D001095:Arachidonic Acids; D016232:Endothelins; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D010959:Tissue Plasminogen Activator; D007213:Indomethacin