Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog.
1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.
McAuliffe
S J
SJ
Bioscience II, ICI Pharmaceuticals, Macclesfield.
Snow
H M
HM
Cox
B
B
Smith
C C
CC
Noble
M I
MI
D000758:Anesthesia; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D011804:Quinolines; D012702:Serotonin Antagonists; D012701:Serotonin; C060632:ICI 170809; D004837:Epinephrine