Regional haemodynamic effects of platelet activating factor in the rat.
The effects of platelet activating factor (PAF) on haemodynamics in the absence and presence of the potent PAF receptor antagonist TCV-309 (3-bromo-5-[N-phenyl-N-[2-[[2-(1,2,3,4-tetrahydro-2- isoquinolyl-carbonyloxy)ethyl]carbamoyl]ethyl]carbamoyl]-1- propylpyridinium nitrate) were studied by the microsphere technique in pentobarbitone-anaesthetized rats. I.v. infusion of the low dose PAF (0.05 microgram kg-1 min-1) did not significantly alter mean arterial pressure, cardiac output or total peripheral resistance but increased arterial conductances in the stomach, intestine, caecum and colon and reduced conductance in the spleen. I.v. infusion of the high dose of PAF (0.3 microgram kg-1 min-1) markedly reduced mean arterial pressure (-53 mm Hg) and cardiac output (-62%) and insignificantly increased total peripheral resistance. Arterial conductances in the lungs, stomach, intestine, caecum and colon, kidneys and spleen were reduced and those in the heart and muscle were increased. TCV-309 (10 micrograms kg-1) abolished all changes in arterial pressure, cardiac output and total peripheral resistance and arterial conductances elicited by either the low or the high dose of PAF. The results show that a non-hypotensive dose of PAF caused vasodilatation of the gastrointestinal organs and vasoconstriction of the spleen. A high dose of PAF which markedly decreased arterial pressure and cardiac output caused vasodilatation of the heart and muscle and vasoconstriction of the lungs (bronchial), gastrointestinal organs, kidneys and spleen. All haemodynamic changes were blocked by TCV-309 indicating the involvement of PAF receptors.
King
K A
KA
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Lim
S L
SL
Pang
C C
CC
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; C067430:TCV 309