J. Anim Sci., doi: 10.2527/jas.2006-803
©Copyright, 2007, The American Society of Animal Science
Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay
J. L. Klotz 1,
L. P. Bush 2,
D. L. Smith 3,
W. D. Shafer 3,
L. L. Smith 1,
B. C. Arrington 2,
J. R. Strickland 1*
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.
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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
