Interaction of isoflavones and endophyte-infected tall fescue seed extract on vasoactivity of bovine mesenteric vasculature

Authors: JIA, YANG - University Of Kentucky; HARMON, DAVID - University Of Kentucky; Flythe, Michael; Klotz, James

Submitted to: Frontiers in Nutrition: Animal Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2015
Publication Date: 10/19/2015
Citation: Jia, Y., Harmon, D.L., Flythe, M.D., Klotz, J.L. 2015. Interaction of isoflavones and endophyte-infected tall fescue seed extract on vasoactivity of bovine mesenteric vasculature. Frontiers in Nutrition: Animal Nutrition and Metabolism. doi: 10.3389/fnut.2015.00032.

Interpretive Summary: Ergot alkaloids have been connected with vasoconstriction-related problems and isoflavones have estrogenic activities that have been associated with vasorelaxation. Thus, it was hypothesized that isoflavones may attenuate ergot alkaloid induced vasoconstriction and possibly alleviate the diminished contractility of mesenteric vasculature after preliminary exposure to ergot alkaloids. The objective of this study was to determine if an incubation of bovine mesenteric vasculature with the isoflavones formononetin or biochanin A, or an ergot alkaloid-containing tall fescue seed extract and the combination of alkaloids and isoflavones affect ergotamine-induced contractility. Of the compounds and concentrations evaluated, the ergot alkaloid-exposed blood vessels were negatively affected and did not respond to subsequent ergotamine-induced stimulation. Conversely, the isoflavones had only minor impacts in offsetting the negative vasoconstrictive effects caused by the ergot alkaloids. However, there was enough of an influence observed that other concentrations of these isoflavones and their downstream metabolites should be investigated. These findings will benefit other scientists trying to understand the role that these offsetting compounds can play in solving ergot-alkaloid related problems in animal agriculture.

Technical Abstract: It was hypothesized that isoflavones may attenuate ergot alkaloid-induced vasoconstriction and possibly alleviate diminished contractility of vasculature after exposure to ergot alkaloids. The objective of this study was to determine if prior incubation of bovine mesenteric vasculature with the isoflavones formononetin (F), biochanin A (B), or an ergovaline-containing tall fescue seed extract (EXT) and their combinations affect ergotamine (ERT) induced contractility. Multiple segments of mesenteric artery and vein supporting the ileal flange of the small intestine were collected from Angus heifers at slaughter (n=5, Bodyweight = 639 ±39 kg). Duplicates of each vessel type were incubated in tissue culture flasks at 37' with a 50-mL volume of Krebs-Henseleit buffer containing: only buffer (Control); or 1 × 10-6 M EXT; F; or B; and combinations of 1 × 10-6 M EXT+F; 1 × 10-6 M EXT+B; 1 × 10-6 M F+B; or 1 × 10-6 M EXT+F+B. After incubation for 2 h, sections were mounted in a multimyograph chamber. The ERT dose responses were normalized to 0.12 M KCl. Pretreatment with F, B, and F+B without EXT resulted in similar contractile responses to ERT in mesenteric artery and all incubations containing EXT resulted in a complete loss of vasoactivity to ERT. In mesenteric artery pretreated with EXT, treatments that contained B had higher contractile responses (P < 0.05) at ERT concentrations of 1 × 10-7 M and 5 × 10-7 M. Also, treatments containing B tended (P < 0.1) to have greater responses than treatments without B at ERT concentrations of 1 × 10-6 M, 5×10-6 M, and 5 × 10-5 M. In mesenteric vein pretreated with EXT, treatments containing F had greater contractile responses to ERT at 1 × 10-5 M, 5 × 10-5 M, and 1 × 10-4 M (P < 0.05). These data indicated that F and B at 1 × 10-6 M and their combination did not impact the overall contractile response to ERT in mesenteric vasculature. However, F and B may offset some of the vasoconstriction caused by prior exposure to ergot alkaloids.