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

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% O-2 + 5% CO2; pH = 7.4; 37 degrees C). The tissue was allowed to equilibrate at 1 g of tension for 90 minbefore of the addition of treatments. Increasing doses of ergovaline (1x10(-11) to 1 x 10(-4) M) or ergotamine (1 x 10(-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 x 10(-4) M). Contractile responses of saphenous veins were similar for ergovaline and ergotamine. Initial contractile responses began at 1 x 10(-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 x 10(-5) M ergotamine; 69.6 +/- 5.3% at 1 x 10(-4) M ergovaline). Interestingly, ergovaline-induced contractions ( 1 x 10(-) (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.