Submitted to: Journal of Animal Science
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/20/2007
Publication Date: 4/1/2008
Citation: Klotz, J.L., Kirch, B.H., Aiken, G.E., Bush, L.P., Strickland, J.R. 2008. Effects of Selected Combinations of Tall Fescue Alkaloids on the Vasoconstrictive Capacity of Fescue-Naive Bovine Lateral Saphenous Veins. Journal of Animal Science. 2008. 86:1021-1028. Interpretive Summary: The types of alkaloids herbivores are exposed to are chemically diverse and have been shown to result in differing vasoconstrictive responses. N-acetylloline (unsaturated pyrrolizidine alkaloid), lysergic acid (ergoline alkaloid), and ergovaline (ergopeptine alkaloid) have individually been shown to generate differing vasoconstrictive responses. Using the bovine lateral saphenous vein bioassay, there did appear to be an additive interaction of the alkaloids when the tissue was exposed to various combinations, as combinations containing 1 × 10-7 M ergovaline did differ from individual concentration responses. N-acetylloline and lysergic acid did not inhibit or potentiate the effects of the ergot alkaloids on vascular activity to any appreciable extent. These findings support the possibility that at least an additive effect may exist and this should be considered when using in vitro bioassays and interpreting resultant data. Further research is needed to investigate the possibility that bioaccumulation of ergovaline could be occurring in this bioassay and in animals consuming endophyte-infected tall fescue.
Technical Abstract: Vasoconstriction is a response associated with consumption of toxic endophyte-infected tall fescue. It is not known if endophyte-produced alkaloids act alone or collectively in mediating the response. Therefore, objective of this study was to examine the vasoconstrictive potentials of selected ergot alkaloids, individually or in paired combinations, using bovine lateral saphenous veins biopsied from fescue-naïve cattle. Segments (2-3 cm) of vein were surgically biopsied from healthy cross-bred yearling heifers (n = 22; 330 ± 8 kg). Veins were trimmed of excess fat and connective tissue, sliced into 2-3 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). Increasing doses of ergovaline, lysergic acid, and N-acetylloline individually or in combination, were evaluated. Contractile data were normalized as a percent of contractile response induced by a reference dose of norepinephrine (1×10-4 M). Increasing concentrations of lysergic acid did not result in an appreciable contractile response until the addition of 1×10-4 M lysergic acid. In contrast, the vascular response to increasing concentrations of ergovaline was apparent at 1×10-8 M and increased to a maximum of 104.2 ± 6.0% with the addition of 1×10-4 M ergovaline. The presence of N-acetylloline did not alter the onset or magnitude of vascular response to either lysergic acid or ergovaline. The presence of 1×10-5 M lysergic acid with increasing concentrations of N-acetylloline and ergovaline generated an increased contractile response during the initial additions compared to the responses of N-acetylloline and ergovaline alone. In the presence of 1×10-7 M ergovaline, the contractile response increased with increasing concentrations of N-acetylloline and lysergic acid. Neither N-acetylloline or lysergic acid elicit a very intense contractile response individually, suggesting that this was the result of the repetitive addition of 1×10-7 M ergovaline. These data indicate that ergovaline is a more potent vascular toxicant than lysergic acid and N-acetylloline. The contractile responses of the ergovaline and lysergic acid combinations did appear to differ from the individual dose-responses. These data support the possibility that an additive alkaloid exposure effect may exist and should be considered during evaluations of ergot alkaloids.