Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay

Authors: Klotz, James; BUSH, LOWELL - UNIV OF KENTUCKY; SMITH, DARRIN - EASTERN KENTUCKY UNIV; SHAFER, WILL - EASTERN KENTUCKY UNIV; Smith, Lori; ARRINGTON, BRAD - UNIV OF KENTUCKY; Strickland, James

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2007
Publication Date: 9/1/2007
Citation: Klotz, J.L., Bush, L.P., Smith, D.L., Shafer, W.D., Smith, L.L., Arrington, B.C., Strickland, J.R. 2007. Ergovaline-induced vasoconstriction in an isolated bovine lateral saphenous vein bioassay. Journal of Animal Science. 85:2330-2336.

Interpretive Summary: Ergovaline has been reported to be the most abundant alkaloid found in endophyte-infected tall fescue. Unfortunately, pure samples of ergovaline are difficult to obtain and has limited research addressing the effects of the alkaloid in animals. Much of the pharmacologic research has been conducted using ergotamine, a chemically similar alkaloid, but produced at much lower levels by the endophyte . Using the bovine lateral saphenous vein bioassay, ergovaline and ergotamine were shown to be potent vasoconstrictors. The concentration responses of ergovaline strongly resembled those of ergotamine. The longevity of the ergovaline-receptor interaction agrees with previous reports using both ergovaline and ergotamine and provides evidence in support of the bioaccumulation hypotheses. Given the abundance of ergovaline in the plant, the potency, and the binding strength of the alkaloid suggest that it would take only minute quantities to elicit a response in the animal and could slowly accumulate over time. These findings provide further evidence of the vascular potency of the ergopeptine alkaloids and provide focus for future research.

Technical 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 (2 to 3 cm) of the cranial branch of lateral saphenous vein were collected from healthy mixed breed cattle (n = 12 and n = 5 for the ergovaline and ergotamine experiments, respectively) at local abattoirs. 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 a modified Krebs-Henseleit oxygenated 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 ergovaline (1 × 10-11 to 1 × 10-4 M) or ergotamine (1 × 10-11 to 1 × 10-5 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 (1 × 10-4 M). Treatment of bovine lateral saphenous veins with increasing concentrations of ergovaline and ergotamine resulted in similar responses. Initial contractile responses began at 1 × 10-8 M for both ergovaline and ergotamine (4.4 ± 0.8% and 5.6 ± 1.1%, respectively). Vascular tension continued to increase as alkaloid concentrations increased to a maximum of 43.7 ± 7.1% for 1 × 10-5 M ergotamine and 69.6 ± 5.3% with the addition of 1 × 10-4 M ergovaline. Interestingly, ergovaline-induced contractions did not appear to relax, with maximal contractile response elicited by 1 × 10-4 M ergovaline not reversed by repeated washing over a 105-min period. Like previously shown with ergotamine, ergovaline is a potent vasoconstrictor. Because ergovaline does not readily wash out, this suggests a potential for bioaccumulation within the animal.