Background: Vascular impairment, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in humans with obesity, insulin resistance or Cushings syndrome. Similar endocrine disorders in horses, resulting in insulin resistance, are associated with laminitis, a dysfunction of the vasculature supplying the hooves, the mechanism of which is unclear. We hypothesised that horses with insulin resistance have both local and systemic evidence of vascular dysfunction.
Methods: In a case control study, healthy horses (n=6) and horses with insulin resistance (n=6) destined for euthanasia were recruited. Small vessels (<1 mm) were harvested from the hooves (laminar artery, laminar vein) and facial skin (facial artery). Vascular function was investigated using wire myography, assessing the response to vasoconstrictors phenylephrine (10−910−5M) and 5-hydroxytryptamine (5HT;10−910−5M) and the vasodilator acetylcholine (10−910−5M).
Results: Laminar arteries and veins and facial arteries from healthy horses contracted in response to KPSS, phenylephrine and 5HT (Emax:laminar arteries>facial arteries>>laminar veins). Laminar veins were more sensitive to 5HT than either laminar arteries or facial arteries (pD2 7.11±0.16 vs 6.47±0.19, P=0.02). Acetylcholine induced a relaxation in all vessels (Emax;laminar arteries>> veins=facial arteries; P=0.02) which was abolished by removal of the endothelium. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in vessels from horses with endocrine disease (% relaxation of healthy laminar arteries 313±94.1% vs diseased 129±14.2%, P=0.014). In addition, contractile responses to phenylephrine (P=0.005) and 5HT (P=0.0007) were increased in laminar veins from horses with endocrine disease; these differences were still apparent following removal of the endothelium. Sensitivity to phenylephrine was reduced (in an endothelium-independent manner) in laminar arteries (P=0.006) and veins (P=0.009) from horses with endocrine disease.
Conclusion: Horses with insulin resistance exhibit significant local and systemic vascular dysfunction. Systemic endothelial dysfunction may be a key determinant of the vascular disease associated with insulin resistance in horses.