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1 Forage-Animal Production Research Unit, USDA-ARS, Lexington, KY 40546
2 Department of Plant and Soil Science, University of Kentucky, Lexington, 40546
3 Department of Chemistry, Eastern Kentucky University, Richmond, KY 40475
* To whom correspondence should be addressed. E-mail: jstrickland{at}ars.usda.gov.
| Abstract |
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Ergovaline has been proposed as a toxic component of endophyte-infected tall fescue. As many of the symptoms of fescue toxicosis are a result of compromised circulation, the objective of this study was to examine the vasoconstrictive potentials of ergovaline and a more documented ergopeptine, ergotamine, using a bovine lateral (cranial branch) saphenous vein bioassay. Segments of the cranial branch of lateral saphenous vein (2 to 3 cm) were collected from healthy mixed breed cattle (n = 12 and n = 5 for the ergovaline and ergotamine experiments, respectively) at local abattoirs. Veins were trimmed of excess fat and connective tissue, sliced into 2- to 3-mm sections and suspended in a myograph chamber containing 5 mL of a modified Krebs-Henseleit oxygenated buffer (95% O2/5% CO2; pH = 7.4; 37°C). Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation of treatment additions. Increasing doses of ergovaline (1 x 10-11 to 1 x 10-4 M) or ergotamine (1 x 10-11 to 1 x 10-5 M) were administered every 15 min following buffer replacement. Contractile response data were normalized as a percent induced by a reference dose of norepinephrine (1 x 10-4 M). Contractile responses of saphenous veins were similar for ergovaline and ergotamine. Initial contractile responses began at 1 x 10-8 M for both ergovaline and ergotamine (4.4 ± 0.8% and 5.6 ± 1.1%, respectively). Vascular tension continued to increase as alkaloid concentrations increased (maximums: 43.7 ± 7.1%, 1 x 10-5 M ergotamine; 69.6 ± 5.3%, 1 x 10-4 M ergovaline). Interestingly, ergovaline-induced contractions (1 x 10-4 M) were not reversed by repeated buffer replacement over a 105-min period. As previously shown with ergotamine, these results confirm ergovaline is a potent vasoconstrictor. The resistance of an ergovaline-induced contraction to relaxation over an extended period of time suggests a potential for bioaccumulation and may aid in understanding its toxicity within the animal.
Key Words: alkaloids, bovine, ergovaline, ergotamine, fescue, vasoconstriction
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