title: Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay.
abstract: Ergovaline has been proposed as a toxic component of endophyte-infected tall fescue. As many of the symptoms of fescue toxicosis are a result of compromised circulation, the objective of this study was to examine the vasoconstrictive potentials of ergovaline and a more documented ergopeptine, ergotamine, using a bovine, lateral (cranial branch) saphenous vein bioassay. Segments of the cranial branch of the lateral saphenous vein (2 to 3 cm) were collected from healthy, mixed breed cattle (n = 12 and n = 5 for the ergovaline and ergotamine experiments, respectively) at local abattoirs. The veins were trimmed of excess fat and connective tissue, sliced into 2- to 3-mm cross sections, and suspended in a myograph chamber containing 5 mL of a modified Krebs-Henseleit, oxygenated buffer (95% O2 + 5% CO2; pH = 7.4; 37 degrees C). The tissue was allowed to equilibrate at 1 g of tension for 90 min before of the addition of treatments. Increasing doses of ergovaline (1x10(-11) to 1 x10(-4) M) or ergotamine (1 x10(-11) to 1 x 10(-5) M) were administered every 15 min after buffer replacement. Contractile response data were normalized to a percentage induced by a reference dose of norepinephrine (1 x10(-4) M). Contractile responses of saphenous veins were similar for ergovaline and ergotamine. Initial contractile responses began at 1 x10(-8) M for both ergovaline and ergotamine (4.4 +/- 0.8% and 5.6 +/-1.1%, respectively). Vascular tension continued to increase as the alkaloid concentrations increased (maximums: 43.7 +/-7.1% at 1 x10(-5) M ergotamine; 69.6 +/- 5.3% at 1 x10(-4) M ergovaline). Interestingly, ergovaline-induced contractions (1 x10(-4) M) were not reversed by repeated buffer replacement over a 105-min period. As previously shown with ergotamine, these results confirm that ergovaline is a potent vasoconstrictor. The resistance of an ergovaline-induced contraction to relaxation over an extended period of time suggests a potential for bioaccumulation of this ergopeptine alkaloid and may aid in understanding its toxicity within the animal.
authors.affiliation: Forage-Animal Production Research Unit, USDA-ARS, Lexington, KY 40546, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Klotz
authors.forename: L P
authors.initials: LP
authors.lastname: Bush
authors.forename: D L
authors.initials: DL
authors.lastname: Smith
authors.forename: W D
authors.initials: WD
authors.lastname: Shafer
authors.forename: L L
authors.initials: LL
authors.lastname: Smith
authors.forename: B C
authors.initials: BC
authors.lastname: Arrington
authors.forename: J R
authors.initials: JR
authors.lastname: Strickland
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods / Q000662:veterinary*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004878:Ergotamine / Q000633:toxicity; D004879:Ergotamines / Q000633:toxicity*; D005260:Female; D008297:Male; D012501:Saphenous Vein / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000633:toxicity*
chemical_list: D004879:Ergotamines; D014662:Vasoconstrictor Agents; C076760:ergovaline; D004878:Ergotamine