title: Vasodilatory effect of pentoxifylline in isolated equine digital veins.
abstract: The direct vasodilatory action of pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) and its signalling pathway was evaluated in equine digital veins. Cumulative concentration-response curves to pentoxifylline (1 nM to 300 μM) were recorded in phenylephrine-precontracted equine digital vein rings under different experimental conditions. Relaxation to pentoxifylline was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (a non-xanthine adenosine receptor antagonist; 3 μM). Nitric oxide synthase (NOS), soluble guanylate cyclase and cyclooxygenase (COX) inhibitors (Nω-nitro-L-arginine methyl ester (100 μM), ODQ (30 μM) and indomethacin (10 μM), respectively) significantly reduced the maximum relaxation induced by pentoxifylline. Moreover, pentoxifylline-induced relaxation was strongly reduced by Rp-8-Br-PET-cyclic guanosine monophosphate-S (a protein kinase G inhibitor; 3 μM), but remained unaffected by H-89 (a protein kinase A inhibitor; 2 μM). Pentoxifylline-induced relaxation was associated with a 3.4-fold increase in tissue cGMP content. To investigate whether pentoxifylline can affect cAMP- and cGMP-mediated relaxations, curves to forskolin, to sodium nitroprusside (SNP) and 8-bromo-cGMP were also recorded in endothelium-denuded equine digital vein rings pretreated with pentoxifylline (10 and 100 μM). Pentoxifylline only potentiated the SNP-mediated relaxation at the highest concentration (100 μM). Thus, pentoxifylline relaxed equine digital veins via endothelium-dependent and endothelium-independent components. The effect was mediated through both the NOS and COX pathways and could also result from inhibition of cGMP specific-phosphodiesterase activity at the highest concentrations used.
authors: LUNAM Université, Oniris, UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle, Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
authors: N
authors: N
authors: Kabbesh
authors: M
authors: M
authors: Gogny
authors: G
authors: G
authors: Chatagnon
authors: J
authors: J
authors: Noireaud
authors: C
authors: C
authors: Thorin
authors: J-C
authors: JC
authors: Desfontis
authors: M Y
authors: MY
authors: Mallem
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006736:Horses / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects*
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D005576:Colforsin; C016276:8-bromocyclic GMP; D006152:Cyclic GMP; D010431:Pentoxifylline; D007213:Indomethacin