Involvement of platelet-activating factor in the modulation of vascular tone in the isolated perfused rabbit kidney.
The hypothesis that platelet-activating factor (PAF) plays a role in the modulation of the vasomotor tone and blood pressure was put forward by our group in previous in vivo studies in anaesthetised rabbits. The present study was undertaken to investigate the putative role of this lipid mediator in the vascular reactivity of the renal circulation, using the experimental model of the isolated perfused rabbit kidney. Dose-response curves to noradrenaline-induced vasoconstriction were performed before and after continuous infusions of two different PAF-receptor antagonists (WEB 2086 and yangambin) and of the phospholipase A2 inhibitor mepacrine. The increases in renal perfusion pressure elicited by noradrenaline were potentiated by all the above-mentioned treatments in a dose-dependent manner. Moreover, prostaglandin F2alpha-induced vasoconstriction was also potentiated by the administration of the PAF receptor antagonists and mepacrine. Furthermore, the administration of PAF into the renal circulation induced dose-related and long-lasting vasodilator responses, which were blocked by the PAF receptor antagonists. Nevertheless, PAF-induced renal vasodilation was also abolished by a pretreatment with mepacrine or with the cyclooxygenase inhibitor indomethacin, suggesting that it enhances the secondary formation of vasodilator arachidonic acid metabolites. The data indicate that PAF is involved in the modulation of the vasomotor tone in the renal circulation, through the release of cyclooxygenase products, constituting an additional mechanism of modulation of smooth muscle cell contractility to the ones exerted by well-known vasoactive substances of endothelial origin such as nitric oxide.
Cailleaux
S
S
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Lopes-Martins
R A
RA
Aimbire
F
F
Cordeiro
R S
RS
Tibiriçá
E
E
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology; D017705:Lignans / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D012079:Renal Circulation / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001381:Azepines; D004791:Enzyme Inhibitors; D005663:Furans; D017705:Lignans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D014662:Vasoconstrictor Agents; C052518:WEB 2086; C082827:epiyangambin; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D009638:Norepinephrine