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.
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.
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.
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.
Conclusion, Clinical Relevance & Take Home Message
High concentrations of insulin may have deleterious effects when endothelial function is compromised.
1Royal Veterinary College, Royal College Street, London, UK
2Faculty of Veterinary Science, University of Melbourne, Victoria 3010, Australia
3Equine Studies Group, WALTHAM Centre for Pet Nutrition, Melton Mowbray, UK
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