Contractile response of fescue-naive bovine lateral saphenous veins to increasing concentrations of tall fescue alkaloids.
Various alkaloids found in endophyte-infected tall fescue have been shown to elicit different effects in the grazing animal. As part of an ongoing characterization of vascular response generated by different alkaloids, the objective of this study was to examine the vasoconstrictive potentials of ergonovine (a simple lysergic acid derivative) and alpha-ergocryptine, ergocristine, and ergocornine (all ergopeptine alkaloids) using bovine lateral saphenous veins (cranial branch) biopsied from fescue-naïve cattle. Segments (2 to 3 cm) of vein were surgically biopsied from healthy crossbred yearling cattle (n = 18; 274 +/- 8 kg of BW). Veins were trimmed of excess fat and connective tissue, sliced into 2 to 3 mm sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation of treatment additions. Increasing doses of each alkaloid (1 x 10(-10) to 1 x 10(-4) M) were administered every 15 min after buffer replacement. Data were normalized as a percentage of contractile response induced by a reference dose of norepinephrine (1 x 10(-4) M). Exposure of vein segments to increasing concentrations of ergocryptine, ergocristine, and ergonovine did not result in a contractile response until 1 x 10(-7) M, and ergocornine was even less potent (P < 0.05). Ergonovine had a greater maximal contractile intensity than ergocristine and ergocryptine (P < 0.05), with the 1 x 10(-4) M responses of ergonovine, ergocristine, ergocryptine, and ergocornine reaching maximums of 68.5 +/- 4.1, 45.5 +/- 4.5, 42.9 +/- 4.1%, and 57.2 +/- 9.9% of the norepinephrine maximum, respectively. The contractile response to increasing concentrations of ergonovine vs. ergocryptine, ergocristine, and ergocornine were opposite from previous evaluations of ergoline (e.g., lysergic acid) and ergopeptine (e.g., ergovaline) alkaloids using this bioassay, where the ergopeptine generated the greater contractile intensity. These data indicate that ergopeptines structurally different only at a single position of the peptide moiety do not exhibit differing contractile responses when considering contractile intensity. This difference may alter the potency when considering ergocornine was less potent than ergocryptine or ergocristine. These alkaloids may need to be considered when evaluating causative agents vasoconstriction associated with tall fescue-induced toxicosis.
Klotz
J L
JL
USDA-ARS, Forage-Animal Production Research Unit, Lexington, KY 40546-0091, USA. james.klotz@ars.usda.gov
Kirch
B H
BH
Aiken
G E
GE
Bush
L P
LP
Strickland
J R
JR
D000818:Animals; D002417:Cattle; D004876:Ergot Alkaloids / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D015394:Molecular Structure; D055328:Neotyphodium / Q000378:metabolism; D006109:Poaceae / Q000382:microbiology*; D012501:Saphenous Vein / Q000187:drug effects*; D046509:Tissue Culture Techniques
D004876:Ergot Alkaloids