Evidence of vascular dysfunction has been found in horses with endocrinopathic laminitis, according to new research.
Endocrinopathic laminitis occurs in association with equine metabolic syndrome and Cushing’s disease.
University of Edinburgh researchers Ruth Morgan, John Keen, Brian Walker and Patrick Hadoke noted that vascular dysfunction — most commonly due to dysfunction in the endothelium, the cells that line the interior surface of blood vessels — was associated with cardiovascular risk in people with metabolic syndrome and Cushing’s syndrome.
As in humans, horses with metabolic syndrome or Cushing’s often had multiple risk factors that are associated with endothelial dysfunction in humans.
The study team tested the hypothesis that horses with endocrinopathic laminitis have vascular, specifically endothelial, dysfunction.
Six healthy horses and six with endocrinopathic laminitis were used in the research.
The scientists studied vessels from the hooves (the laminar artery and laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. They tested their response to the blood vessel constrictors phenylephrine and 5-hydroxytryptamine (5HT); and the vessel dilator acetylcholine.
In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with endocrinopathic laminitis.
In addition, the contractile responses to phenylephrine and 5HT were higher in intact laminar veins from horses with endocrinopathic laminitis compared with healthy horses.
These differences were endothelium-independent, they say.
Sensitivity to phenylephrine was reduced in intact laminar arteries and veins from horses with endocrinopathic laminitis.
“Horses with endocrinopathic laminitis exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries,” the study team reported in the open-access peer-reviewed journal, PLOS ONE.
“The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof.”
The authors say their work demonstrated that horses with endocrinopathic laminitis had vascular dysfunction that manifests as blunting of endothelium-dependent vasodilation, present in both the laminar vascular bed and distant facial skin arteries.
“In addition, laminar veins of endocrinopathic laminitis horses showed further dysfunction with increased contractile responses to phenylephrine and 5HT, accompanied by a decrease in sensitivity to phenylephrine.”
Discussing their findings, the researchers said: “It is important to note that, even though vessels from endocrinopathic laminitis horses relaxed significantly less than those from healthy horses, the arteries still relaxed by 100% whereas the mean relaxation of the veins was only 70%.
“This most likely reflects endothelial dysfunction of the veins but, in the arteries, a loss of intrinsic tone may also play a role. It is important to note that the dysfunction identified in this study could be a cause or a consequence of disease.”
They continued: “Failure of the vessels within the hoof to adequately dilate will have significant consequences, potentially reducing overall blood flow and reducing venous return. Such abnormalities may lead to increased capillary pressure and oedema and hypoxia of the laminar tissue. Equally, systemic endothelial dysfunction may render these animals susceptible to other vascular and microvascular abnormalities such as retinal vascular lesions not previously investigated in this population.”
They said clinical vascular markers of endothelial dysfunction such as flow mediated dilatation may not be readily transferrable to equine medicine. However, plasma biomarkers of endothelial dysfunction, such as asymmetrical dimethylarginine and oxidized LDL, would be an invaluable clinical tool for determining laminitic risk and monitoring response to treatment.
The study team noted that pharmacological interventions aimed at restoring blood flow to the hoof had been used clinically with varying success, possibly reflecting our limited understanding of vascular dysfunction in laminitis.
“Given the high prevalence of this disorder and the clinical consequences there is still an urgent unmet clinical need in this area of veterinary medicine.”
The endothelium may be a target for the treatment or diagnosis of endocrinopathic laminitis, the researchers says.
Morgan RA, Keen JA, Walker BR, Hadoke PWF (2016) Vascular Dysfunction in Horses with Endocrinopathic Laminitis. PLoS ONE 11(9): e0163815. doi:10.1371/journal.pone.0163815
