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ANIMAL PRODUCTION |
* Forage-Animal Production Research Unit, USDA-ARS, Lexington, KY 40546;
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Department of Chemistry, Eastern Kentucky University, Richmond 40475;
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Department of Plant and Soil Science, University of Kentucky, Lexington 40546;
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Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis 97331
2 Corresponding author: jstrickland{at}ars.usda.gov
Vasoconstriction has been associated with several symptoms of fescue toxicosis thought to be alkaloid induced. Lysergic acid, an ergot alkaloid, has been proposed as a toxic component of endophyte-infected tall fescue. The objective of this study was to examine the vasoconstrictive potential of D-lysergic acid using a bovine lateral (cranial branch) saphenous vein bioassay. Before testing lysergic acid, validation of the bovine lateral saphenous vein bioassay for use with a multimyograph apparatus was conducted using a dose-response to norepinephrine to evaluate the effects of limb of origin (right vs. left) and overnight storage on vessel contractile response. Segments (2 to 3 cm) of the cranial branch of the lateral saphenous vein were collected from healthy mixed breed cattle (n = 12 and n = 7 for the lysergic acid and norepinephrine experiments, respectively) at local abattoirs. Tissue was placed in modified Krebs-Henseleit, oxygenated buffer and kept on ice or stored at 2 to 8°C until used. 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 oxygenated Krebs-Henseleit 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 norepinephrine (1 x 10–8 to 5 x 10–4 M) or lysergic acid (1 x 10–11 to 1 x 10–4 M) were administered every 15 min after buffer replacement. Data were normalized as a percentage of the contractile response induced by a reference dose of norepinephrine. Veins from both left and right limbs demonstrated contractions in a dose-dependent manner (P < 0.01) but did not differ between limbs. There were no differences in dose-response to norepinephrine between tissue tested the day of dissection and tissue tested 24 h later. Exposure of vein segments to increasing concentrations of lysergic acid did not result in an appreciable contractile response until the addition of 1 x 10–4 M lysergic acid (15.6 ± 2.3% of the 1 x 10–4 M norepinephrine response). These data indicate that only highly elevated concentrations of lysergic acid result in vasoconstriction. Thus, in relation to the symptoms associated with vasoconstriction, lysergic acid may only play a minor role in the manifestation of fescue toxicosis.
Key Words: alkaloid • bovine • fescue • lysergic acid • vasoconstriction
This article has been cited by other articles:
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  J. L. Klotz, B. H. Kirch, G. E. Aiken, L. P. Bush, and J. R. Strickland Effects of selected combinations of tall fescue alkaloids on the vasoconstrictive capacity of fescue-naive bovine lateral saphenous veins J Anim Sci, April 1, 2008; 86(4): 1021 - 1028. [Abstract] [Full Text] [PDF]
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J. L. Klotz, L. P. Bush, D. L. Smith, W. D. Shafer, L. L. Smith, B. C. Arrington, and J. R. Strickland Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay J Anim Sci, September 1, 2007; 85(9): 2330 - 2336. [Abstract] [Full Text] [PDF]
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