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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication Date: 2011-10-08 PubMed ID: 21986319DOI: 10.1016/j.tvjl.2011.09.005Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates the vasodilatory effects of the drug pentoxifylline on isolated equine (horse) digital veins. The effects were broken down by various levels of drug concentration and different experimental conditions, while the drug’s interaction with various inhibitors was also studied.
Methodology
- The study used isolated equine digital vein rings and applied varying concentrations of pentoxifylline, from 1 nanometer to 300 micrometers.
- These veins were precontracted using a drug called phenylephrine.
- To understand the signalling pathway, the research assessed how inhibiting substances, such as nitric oxide synthase (NOS), soluble guanylate cyclase and cyclooxygenase (COX) evolve the overall response.
- The effects of removing the endothelium, the lining of the blood vessels, were also documented.
Findings
- Relaxation of veins was seen to be partially affected by the removal of the endothelium, indicating that pentoxifylline has both endothelium-dependent and independent vasodilatory components.
- The removal of the endothelium did not alter the effects of CGS-15943, an adenosine receptor antagonist, thereby proving that the vasodilatory effect is not mediated by the adenosine receptors.
- The use of various inhibitors, such as NOS, soluble guanylate cyclase and COX significantly reduced the maximum relaxation induced by pentoxifylline, indicating their role in the process.
- The relaxation effect of pentoxifylline was strongly reduced by Rp-8-Br-PET-cyclic guanosine monophosphate-S, a protein kinase G inhibitor, but remained unaffected by H-89, a protein kinase A inhibitor.
Conclusions
- Pentoxifylline seems to relax equine digital veins through multiple pathways. It appears to function through both endothelium-dependent and endothelium-independent components.
- The vasodilatory effect acts through pathways involving NOS and COX and also potentially inhibits cGMP specific-phosphodiesterase activity, especially at the highest concentrations used in the study.
Cite This Article
APA
Kabbesh N, Gogny M, Chatagnon G, Noireaud J, Thorin C, Desfontis JC, Mallem MY.
(2011).
Vasodilatory effect of pentoxifylline in isolated equine digital veins.
Vet J, 192(3), 368-373.
https://doi.org/10.1016/j.tvjl.2011.09.005 Publication
Researcher Affiliations
- LUNAM Université, Oniris, UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle, Atlanpole La Chantrerie, BP 40706, Nantes F-44307, France.
MeSH Terms
- Animals
- Colforsin / pharmacology
- Cyclic GMP / analogs & derivatives
- Cyclic GMP / pharmacology
- Dose-Response Relationship, Drug
- Endothelium, Vascular / physiology
- Horses / physiology
- Indomethacin / pharmacology
- Nitroprusside / pharmacology
- Pentoxifylline / pharmacology
- Tissue Culture Techniques
- Vasodilation / drug effects
- Vasodilator Agents / pharmacology
- Veins / drug effects
Citations
This article has been cited 4 times.- Broekhuizen M, de Vries R, Smits MAW, Dik WA, Schoenmakers S, Koch BCP, Merkus D, Reiss IKM, Danser AHJ, Simons SHP, Hitzerd E. Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.. Br J Pharmacol 2022 Nov;179(22):5074-5088.
- Al-Nimer M, Ratha R, Mahwi T. Pentoxifylline improves the quality of life in type-2 diabetes foot syndrome.. Pak J Med Sci 2019 Sep-Oct;35(5):1370-1375.
- Stokol T, Serpa PBS, Zahid MN, Brooks MB. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation.. Front Vet Sci 2016;3:99.
- Azhar A, El-Bassossy HM. Pentoxifylline alleviates hypertension in metabolic syndrome: effect on low-grade inflammation and angiotensin system.. J Endocrinol Invest 2015 Apr;38(4):437-45.
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