Effects of tumor necrosis factor on in vitro digital arterial responses in horses.
Authors: Baxter
Journal: American journal of veterinary research
Summary
# Editorial Summary Endotoxaemia is known to impair vascular function in horses with conditions such as laminitis and sepsis, but the precise cellular mechanisms driving these changes remain incompletely understood. Baxter investigated whether tumour necrosis factor (TNF), a key inflammatory cytokine released during endotoxic shock, could directly cause the vascular dysfunction observed clinically by examining palmar digital artery rings from six horses in isolated tissue bath preparations, exposing them to TNF at physiologically relevant concentrations (5,100 pg/ml) and measuring their contractile and relaxant responses to various agonists including acetylcholine, bradykinin, norepinephrine and serotonin. TNF exposure significantly impaired endothelium-dependent relaxation to acetylcholine and augmented maximal contraction to norepinephrine, demonstrating that the inflammatory cytokine itself is sufficient to replicate the vascular pathology seen in vivo; however, TNF supplementation with L-arginine (a nitric oxide precursor) did not reverse these changes, suggesting the dysfunction may involve mechanisms beyond simple nitric oxide depletion. The findings were concentration-independent, as 10-fold higher TNF concentrations produced identical results, and responses to bradykinin and serotonin remained unaffected across all treatment groups. For practitioners managing endotoxaemic or systemically inflammatory horses, these results underscore how inflammatory mediators directly compromise digit perfusion through multiple vascular mechanisms, potentially explaining the rapid deterioration of digital blood flow in conditions like acute laminitis and supporting the clinical rationale for aggressive anti-inflammatory and endotoxin-neutralising strategies in the critical early phase of these conditions.
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Practical Takeaways
- •TNF appears to be a key mediator of endotoxin-induced vascular dysfunction in equine digital arteries, potentially contributing to digital ischemia and laminitis pathophysiology
- •L-arginine supplementation alone does not counteract TNF-mediated endothelial dysfunction in this model, suggesting more targeted therapeutic approaches may be needed
- •Understanding TNF's role in endotoxemia-related vascular changes may help develop preventative or therapeutic strategies for endotoxic horses at risk of laminitis
Key Findings
- •TNF exposure significantly decreased maximal relaxation to acetylcholine in palmar digital arteries (P = 0.04)
- •TNF exposure significantly increased maximal contraction to norepinephrine compared to control (P = 0.04)
- •L-arginine co-treatment did not reverse TNF-induced vascular dysfunction
- •TNF did not alter vascular responses to bradykinin or serotonin