The effects of PAF-acether on the cardiovascular system and their inhibition by a new highly specific PAF-acether receptor antagonist BN 52021.
BN 52021, a new specific PAF-acether receptor antagonist, was evaluated on several cardiovascular models. BN 52021 antagonized PAF-acether-induced extravasation in rats. Inhibition of the hypotensive action of PAF-acether was obtained by administration of the antagonist, given preventively or curatively. In isolated guinea-pig hearts, BN 52021 inhibited the vasoconstriction induced by PAF-acether whereas a small inhibition was observed with papaverine. On the other hand, phosphodiesterase inhibitors were very effective against coronary vasoconstriction induced by vasopressin while BN 52021 was without effect. PAF-acether increased the tonus of rat isolated portal vein; this effect was inhibited by BN 52021, without any reduction in basal myogenic activity. In this model Ca2+ antagonists (D 600, diltiazem) showed a small inhibitory effect but they strongly reduced basal myogenic activity. Neither PAF-acether nor BN 52021 modified phenylephrine-induced contraction of the isolated rabbit aorta with or without endothelium demonstrating that endothelium-dependent relaxing factor is not related to PAF-acether. Our results suggest that BN 52021 specifically block the cardiovascular effects of PAF-acether. This agent may thus be an useful tool for a better understanding of the role of PAF-acether in hemodynamic changes involved in anaphylaxis or shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004224:Diterpenes; D004336:Drug Antagonism; D046934:Ginkgolides; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D007783:Lactones; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B