title: The acute increases in vasomotor tone and blood pressure induced by carotid artery occlusion are modulated by platelet-activating factor (PAF) independently of nitric oxide release.
abstract: The purpose of the present study was to investigate the involvement of nitric oxide (NO) in the modulatory role of platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a vasoactive phospholipid mediator synthesized by endothelial cells, on the vascular tone and arterial blood pressure. In pentobarbitone-anaesthetized rabbits, unloading of the carotid sinus baroreceptors by a bilateral carotid artery occlusion elicited a reflex rise in systemic vascular resistance, which was markedly potentiated by pretreating the animals with the PAF receptor antagonist WEB 2086 ([3-4-(2-chlorphenyl-)-9-methyl-6H-thieno-3,2-f-1,2,4-triazolo-4,3 -alpha-1,4 -diazepin-2-yl-(4-morpholinyl)-1-propanone]; 5 mg/kg, i.v.). In contrast, the inhibition of the biosynthesis of NO via NO synthase using N omega-nitro-L-arginine methyl ester (L-NAME) neither affected the systemic vasoconstriction induced by carotid artery occlusion nor modified the potentiating effect of WEB 2086. The haemodynamic alterations induced by L-NAME administration were corrected by continuous infusions of the directly-acting vasodilators sodium nitroprusside or diazoxide. The results of the present study confirm previous studies from our group suggesting the involvement of PAF in a negative feedback mechanism effective in the local regulation of vasomotor tone in anaesthetized rabbits, but exclude the participation of NO in this process.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Lopes-Martins
authors.forename: V
authors.initials: V
authors.lastname: Estato
authors.forename: C V
authors.initials: CV
authors.lastname: Araújo
authors.forename: M
authors.initials: M
authors.lastname: Catelli
authors.forename: R S
authors.initials: RS
authors.lastname: Cordeiro
authors.forename: E
authors.initials: E
authors.lastname: Tibiriçá
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D016893:Carotid Stenosis / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011311:Pressoreceptors / Q000502:physiology; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester