The endothelin ETB receptor agonist, IRL 1620, causes vasodilatation and inhibits ex vivo platelet aggregation in the anaesthetised rabbit.
The ETB receptor agonist, IRL 1620 injected into the left ventricle, induced a biphasic (transient fall followed by a secondary fall lasting 5 min) depressor response in the anaesthetised rabbit. This was followed by a rise in systemic blood pressure which returned to control levels within 30 min. In addition, IRL 1620 caused a strong, transient inhibition of ADP-induced platelet aggregation ex vivo. The selective ETA receptor antagonist, FR 139317 had no effect on either the haemodynamic or anti-aggregatory effects of IRL 1620. Indomethacin which had no effect on the initial transient depressor response induced by IRL 1620, abolished the secondary fall revealing a sustained pressor response. Indomethacin also prevented the IRL 1620-induced inhibition of platelet aggregation ex vivo. Thus, IRL 1620 is a selective ETB receptor agonist in the anaesthetised rabbit, causing vasodilatation, vasoconstriction and inhibition of ex vivo platelet aggregation. The inhibition of platelet aggregation by IRL 1620 is due to an ETB receptor-mediated release of prostacyclin into the circulation, for it is inhibited by indomethacin, but not by FR 139317.
McMurdo
L
L
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Thiemermann
C
C
Vane
J R
JR
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D017466:Receptors, Endothelin / Q000819:agonists*; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D017466:Receptors, Endothelin; C074308:sovateltide