Cardiovascular alterations in the rabbit infused with platelet activating factor (PAF): effect of kadsurenone, a PAF-receptor antagonist.
The ECG and haemodynamic alterations caused by the i.v. infusion of platelet-activating factor (PAF) in the rabbit were studied after pretreatment with Kadsurenone, a specific PAF-receptor antagonist. Infusion of PAF at 0.8 microgram/kg in the rabbit caused important ECG changes, such as ST-segment depression and conduction arrhythmias, concomitantly with a marked reduction in left ventricular systolic pressure, mean arterial pressure and cardiac output, with a rise in total peripheral resistances and mean right atrial pressure. These physiological parameters became maximal at 75-120 seconds after PAF challenge, and returned to near prechallenge values within 25-60 minutes. Pretreatment with Kadsurenone, administered either intravenously (0.014 M, 1 ml/kg) or intraperitoneally (0.14 M, 1 ml/kg), exerted a quite complete protective effect in regard to the ECG changes and caused a significant reduction in the magnitude of all the haemodynamic alterations observed after intravenous infusion of PAF (0.8 microgram/kg). These results suggest that Kadsurenone is an effective inhibitor of PAF-induced cardiovascular changes in the rabbit, probably due to its competitive antagonism against PAF binding to specific receptors.
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D017705:Lignans; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled
D001572:Benzofurans; D017705:Lignans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C044540:kadsurenone