Modulation of Endothelium-Dependent Relaxation of Equine Digital Arteries By Insulin and Hypoxia

Article Outline

• Introduction
• Materials & Methods
• Results
• Discussion
• Conclusion, Clinical Relevance & Take Home Message
• Copyright

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Introduction 

Increasing evidence suggests that phenotypic traits associated with equine metabolic syndrome, such as insulin resistance, could lead to endothelial dysfunction contributing to the pathogenesis of laminitis.

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Materials & Methods 

Rings of equine digital arteries (EDA) were obtained from adult mixed breed horses (n = 4-6) euthanased at an abattoir, for reasons other than research, and were prepared for isometric tension recordings in organ baths. The effect of insulin (1500 μIU/ml) on carbachol (CCh)-induced endothelium-dependent relaxation was examined in EDAs under normoxic (95%O₂/5%CO₂) and hypoxic (95% N₂/5%CO₂) conditions, in the absence or presence of L-NAME (nitric oxide synthase inhibitor, 100 μM) or high extracellular potassium (to inhibit endothelium-derived hyperpolazing factor, EDHF-mediated responses). CCh-induced relaxations were compared using two-way ANOVA.

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Results 

CCh-induced relaxations were not significantly affected by high concentrations of insulin under normoxic conditions but were significantly inhibited by insulin under hypoxic conditions (15% inhibition; P<0.001). In the presence of L-NAME, CCh-induced relaxations were significantly inhibited by hypoxia (40% inhibition; P<0.01) and the inhibition was further exaggerated by insulin; whereas the hypoxia and/or insulin responses were not affected by high extracellular potassium. Control responses were not affected by hypoxia, in the absence of insulin.

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Discussion 

These results suggest that inhibition of CCh-induced relaxation of EDAs by acute exposure of insulin and hypoxia is due to inhibition of the EDHF-mediated component of endothelium-dependent relaxation. The nitric oxide pathway does not appear to be affected by insulin and hypoxia, under conditions of the present study.

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Conclusion, Clinical Relevance & Take Home Message 

High concentrations of insulin may have deleterious effects when endothelial function is compromised.