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This Article Full Text (PDF) All Versions of this Article: jas.2008-1692v1 87/7/2437    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Klotz, J. L. Articles by Strickland, J. R. Search for Related Content PubMed PubMed Citation Articles by Klotz, J. L. Articles by Strickland, J. R.

Bioaccumulation of ergovaline in bovine lateral saphenous veins in vitro

J. L. Klotz^*, B. H. Kirch^*, G. E. Aiken^*, L. P. Bush and J. R. Strickland^*

^* USDA-ARS, Forage-Animal Production Research Unit, Lexington, KY, 40546 Department of Plant and Soil Sciences, University of Kentucky, Lexington, 40546

james.klotz{at}ars.usda.gov

Abstract

Ergot alkaloids have been associated with vasoconstriction in grazing livestock affected by the fescue toxicosis syndrome. Previous in vitro investigations studying how ergot alkaloids caused vasoconstriction have shown that ergovaline has a distinct receptor affinity and sustained contractile response. A similar contractile response has not been noted for lysergic acid. The objectives of this study were to determine if repetitive in vitro exposure of bovine lateral saphenous vein to either lysergic acid or ergovaline would result in an increasing contractile response and if a measurable bioaccumulation of the alkaloids in the vascular tissue occurs over time. Segments of vein were either surgically biopsied from healthy, AngusxBrangus cross-bred, fescue-naïve yearling heifers (n=16) or collected from healthy mixed breed and gender cattle immediately after slaughter (n=12) at a local abattoir. Veins were trimmed of excess fat and connective tissue, sliced into cross-sections and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O₂/5% CO₂; pH = 7.4; 37°C). Contractile responses to repetitive additions of ergovaline (1x10^-9 and 1x10^-7 M) and lysergic acid (1x10^-5 and 1x10^-4 M) were evaluated using the biopsied veins. For the bioaccumulation experiments, veins collected at the abattoir underwent repetitive additions of 1x10^-7 M ergovaline and 1x10^-5 M lysergic acid and the segments were removed after every 2 additions and media rinses for alkaloid quantification via HPLC/MS. Contractile data were normalized as a percent of contractile response induced by a reference dose of norepinephrine (1x10^-4 M). Repetitive additions of 1x10^-9 M ergovaline and 1x10^-5 and 1x10^-4 M lysergic acid resulted in contractile response with a negative slope (P < 0.02). In contrast, repetitive addition of 1x10^-7 M ergovaline resulted in a contractile response that increased with each addition (P < 0.01). Lysergic acid and ergovaline were detected at all 4 exposure levels (2x to 8x), but only the 1x10^-7 M ergovaline treatment resulted in increased tissue content as the number of exposures increased (P < 0.05). These data indicate that ergovaline, but not lysergic acid bioaccumulates with repetitive exposure in vitro. These results suggest that ergovaline may have a greater potential for inducing toxicosis in grazing animals than lysergic acid because of its potential to bioaccumulate at the cellular site of action.

Key Words: bovine • ergovaline • lysergic acid • tall fescue • vasoconstriction