Submitted to: International Symposium on Fungal Endophytes of Grasses
Publication Type: Proceedings
Publication Acceptance Date: 9/5/2006
Publication Date: 3/23/2007
Citation: Klotz, J.L., Kirch, B.H., Aiken, G.E., Bush, L.P., Strickland, J.R., Arrington, B.C. 2007. Assessment of Vasoconstrictive Capacity of Tall Fescue Alkaloids Using Fescue Naive Lateral Saphenous Veins of Crossbreed Heifer Cattle. Proceedings of the 6th International Symposium on Fungal Endophytes of Grasses. Grassland Research and Practice Series No. 13:383-385. Interpretive Summary:
Technical Abstract: Vasoconstriction is one response associated with consumption of toxic endophyte-infected tall fescue. Because it is not known if endophyte-produced alkaloids act alone or collectively, the objective of this study was to begin to examine the vasoconstrictive potentials of D-lysergic acid (LSA), ergovaline (ERV), and N-acetylloline (NAL) 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 cattle (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). Tissue was allowed to equilibrate at 1 g of tension for 90 min prior to initiation of treatment additions. Increasing doses of ERV, LSA, and NAL (1x10-11 to 1x10-4 M) individually or combination (when in combination, LSA and NAL were held constant at 1x10-5 M and ERV at 1x10-7 M) were administered every 15 min following buffer replacement. Data were normalized as a percent of contractile response induced by a reference dose of norepinephrine (1x10-4 M). Increasing concentrations of LSA did not result in an appreciable contractile response until the addition of 1x10-4 M LSA (22.6 ' 4.1%). A vascular response to increasing concentrations of ERV was apparent at 1x10-8 M (4.7 ' 2.2%) and increased to a maximum of 104.2 ' 6.0% with the addition of 1x10-4 M ERV. The presence of NAL did not alter the onset or magnitude of vascular response to either LSA or ERV (maximum responses of 24.9 ' 4.5 and 101.5 ' 10.9%, respectively). The presence of LSA seemed to generate a higher response in the initial additions (1x10-11 M) of NAL and ERV compared to the individual additions, but in the case of NAL the contractile response declined with each subsequent addition. In the presence of 1x10-7 M ERV, the contractile response increased with increasing concentrations of NAL and LSA (maximum responses of 46.3 ' 6.4 and 36.9 ' 5.9%, respectively). Neither of these alkaloids elicit a very intense contractile response individually, suggesting that this could be the result of the repetitive addition of 1x10-7 M ERV. These data indicate that ERV is a more potent vascular toxicant than LSA and NAL. Further, the presence of NAL did not inhibit or potentiate the effects of the ergot alkaloids on vascular activity. The contractile responses of the remaining combinations did appear to differ from the individual dose-responses. This supports the possibility that a combinatorial or repetitive alkaloid exposure effect may exist in vivo and should be considered during in vitro evaluations of ergot alkaloids.