Tall fescue ergot alkaloids are vasoactive in equine vasculature

Authors: Klotz, James; MCDOWELL, KAREN - University Of Kentucky

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/2017
Publication Date: 11/1/2017
Citation: Klotz, J.L., McDowell, K.J. 2017. Tall fescue ergot alkaloids are vasoactive in equine vasculature. Journal of Animal Science. 95(11):5151-5160.

Interpretive Summary: Exposure to ergot alkaloids, fungal toxins found in contaminated grain and grass like tall fescue with fungal endophytes, cause a number of reproductive problems in horses. Other work has shown that ergot alkaloids do cause effects inhibiting blood flow to other non-reproductive areas of the body such as the legs. This study sought to profile the activity of ergot alkaloids in equine blood vessels. The palmar artery and vein were used as models for leg blood vessels and the uterine artery was used as a model for reproductive blood vessels. This was the first time ergovaline, lysergic acid, ergocryptine, ergocornine, and ergocristine activities have been evaluated in equine blood vessels. All ergot alkaloids were active in palmar artery and vein preparations except for lysergic acid. Ergovaline was more active than any of the other ergot alkaloids evaluated. The results of this work demonstrate that vasoconstriction can occur in equine peripheral vasculature, but horses may exhibit signs of exposure differently than cattle. Conversely, ergotamine and ergonovine were minimally active in uterine artery preparations suggesting that effects of ergot alkaloids on fetal development may not be a consequence of restricted blood flow. Animal scientists, veterinarians and horse owners alike will benefit from the this work, as it demonstrates that the effects of ergot alkaloids are not limited to reproductive issues in horses and this should be taken into consideration when researching or diagnosing other other equine issues such as laminitis.

Technical Abstract: Mares grazing endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) typically exhibit reproductive dysfunction rather than problems associated with peripheral vasoconstriction as a primary sign of the fescue toxicosis syndrome. Research using Doppler ultrasonography demonstrated that consumption of endophyte-infected tall fescue seed causes measurable vasoconstriction in the medial palmar artery. The objective of this study was to evaluate contractile responses of medial palmar artery and vein to increasing concentrations of various tall fescue alkaloids. Medial palmar artery and vein were collected immediately following euthanasia from 23 horses of mixed breed, age and gender from both forelimbs and uterine arteries were collected from females (n = 12). Vessels were separated, cleaned of excess connective and adipose tissue, divided into 2-3 mm cross-sections and suspended in a multi-myograph chamber with continuously oxygenated Krebs-Henseleit buffer (95%O2/5%CO2; pH=7.4; 37°C). Following a 90-min equilibration and recovery from reference compound exposure, increasing concentrations of norepinephrine, 5-hydroxytryptamine, ergotamine, and ergonovine for palmar artery and vein and uterine artery and ergovaline, ergocryptine, ergocristine, ergocornine, and lysergic acid for palmar artery and vein were added to assess vasoactivity. Data were normalized as a % contractile response induced by the reference compound addition and analyzed as a completely randomized design. Both norepinephrine and serotonin were vasoactive in all three types of blood vessel. Neither ergotamine nor ergonovine were vasoactive in uterine artery. All alkaloids tested with palmar artery and vein produced a contractile response, except neither palmar artery nor vein responded to LSA (P > 0.05). Ergovaline was the most vasoactive ergot alkaloid in both palmar artery and vein (P < 0.05) followed by ergonovine, whereas out of the 4 remaining ergopeptine alkaloids tested ergocristine induced the lowest contractile response. Although horses do not outwardly appear to be affected by peripheral vasoconstriction as observed in cattle, these data indicate that tall fescue alkaloids are vasoactive and suggest that potential exists for peripheral vascular effects of tall fescue alkaloids in horses. This does not appear to be the case for uterine artery and future research should be directed at understanding how ergot alkaloids cause equine reproductive dysfunction.