title: Constriction of bovine vasculature caused by endophyte-infected tall fescue seed extract is similar to pure ergovaline.
abstract: Ergovaline has been extensively used to study vasoactive effects of endophyte- (Neotyphodium coenophialum) infected tall fescue (Lolium arundinaceum). However, initial results indicated that an extract of toxic tall fescue seed (E+EXT) is more potent than ergovaline alone in a right ruminal artery and vein bioassay. The E+EXT induced a greater contractile response than an equal concentration of ergovaline alone in the ruminal artery of heifers (P = 0.018). This led to a hypothesis that other compounds in the seed extract contribute to vasoconstriction. Thus, experiments were conducted to determine if vasoactivity of an E+EXT is different from a mixture of ergot alkaloids (ALK; ergovaline, ergotamine, ergocristine, ergocryptine, ergocornine, ergonovine, and lysergic acid) of similar concentrations and to determine if the vasoactivity of an E+EXT differs from an endophyte-free tall fescue seed extract (E-EXT). Segments of lateral saphenous vein and right ruminal artery and vein were collected from Holstein steers (n = 6) shortly after slaughter. Vessels were cleaned of excess connective tissue and fat and sliced into segments that were suspended in a multimyograph chamber with 5 mL of continually oxygenated Krebs-Henseleit buffer, equilibrated for 90 min, and exposed to a reference compound (120 mM KCl for ruminal vessels and 0.1 mM norepinephrine for saphenous vein). Increasing concentrations of each treatment (E+EXT, E-EXT, ALK, and ergovaline) were added to the respective chamber every 15 min after buffer replacement. Data were normalized as a percentage of maximal contractile response of the reference compound and fit to a sigmoidal concentration response curve. Ergovaline, ALK, and E+EXT induced similar responses in the saphenous vein, ruminal artery, and ruminal vein. The E+EXT displayed a smaller EC(50) (half maximal effective concentration) than ergovaline or ALK in the saphenous vein and ruminal vein (P < 0.008), but not the ruminal artery (P = 0.31). Extrapolated maximum response was greatest in the saphenous vein for ergovaline, least for E+EXT, and intermediate for ALK (P < 0.0001). The E-EXT did not induce a contractile response in any vessel tested (P > 0.1). Data from this study indicate that ergovaline is largely responsible for the locally induced vasoconstriction of bovine vasculature observed with endophyte-infected tall fescue.
authors.affiliation: Department of Animal and Food Sciences, University of Kentucky, Lexington 40546-0215, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Foote
authors.forename: D L
authors.initials: DL
authors.lastname: Harmon
authors.forename: K R
authors.initials: KR
authors.lastname: Brown
authors.forename: J R
authors.initials: JR
authors.lastname: Strickland
authors.forename: K R
authors.initials: KR
authors.lastname: McLeod
authors.forename: L P
authors.initials: LP
authors.lastname: Bush
authors.forename: J L
authors.initials: JL
authors.lastname: Klotz
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects; D002417:Cattle; D004879:Ergotamines / Q000737:chemistry / Q000494:pharmacology*; D008129:Lolium / Q000382:microbiology*; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012417:Rumen / Q000098:blood supply; D012501:Saphenous Vein / Q000187:drug effects*; D012639:Seeds / Q000382:microbiology*; D014662:Vasoconstrictor Agents / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004879:Ergotamines; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; C076760:ergovaline