Contractile response of fescue-naïve bovine lateral saphenous veins to increasing concentrations of tall fescue alkaloids1,2

Abstract

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.

Effect of Ergopeptines Associated with Tall Fescue Ingestion on Recovery of Horses Subjected to Standardized Exercise Tests

“…These findings are in agreement with those reported by a previous study using the same anaerobic SET where horses were fed ergot alkaloidsecontaining fescue seed obtained from Oregon [3]. There were some differences in the results of this study and those previously reported, in that some studies have reported significant differences in RTs, whereas others have reported no effect on that variable [13].…”

“…In an effort to minimize environmental differences between SET and test days within SET, three horses from group A and two from group B were randomly grouped (group 1) to test on 1 day and vice versa (group 2) on the next SET day. On Mondays, all horses performed a 20-minute aerobic exercise consisting of a walk, trot, and lope (WTL) exercise regimen that included flexion, stops, turns, and backing drills, similar to those used for training, conditioning, and improving strength and agility in most performance horses [3]. This same workout was performed by group 1 on Tuesday and Thursday and by group 2 on Wednesday and Friday, alternating by week so that in the following week, group 1 performed the aerobic work on Wednesday and Friday and group 2 on Tuesday and Thursday.…”

“…Although this fungus bestows drought tolerance and insect resistance to the plant, it also results in the production of the ergot alkaloid ergovaline, which has been identified as the causative agent of fescue toxicosis [2]. In addition, much of the fescue in Missouri is also infected with another fungus Claviceps purpurea that infects the seed head and produces high levels of several ergot alkaloids, including ergovaline and ergotamine, both of which have been shown to be potent vasoconstrictive agents [3]. Numerous studies have been conducted on the effects of ergot alkaloid consumption and cattle performance.…”

Ergovaline, an endophytic alkaloid. 1. Animal physiology and metabolism

“…serotonin, norepinephrine and dopamine) allows ergopeptide alkaloids to interact with an array of different receptors (Berde 1980). It is thought that the variations in the structure of the peptide associated with the ergoline ring is what affects the potency and efficacy of the ergopeptide alkaloid (Klotz et al 2010). In the case of ergovaline, this consists of alanine, proline and valine.…”

Acute exposure to ergot alkaloids from endophyte-infected tall fescue does not alter absorptive or barrier function of the isolated bovine ruminal epithelium

“…The structure of ergocristine is similar to ergovaline with the same basic tricyclic peptide group that only differs at two points (Klotz et al, 2010, Foote et al, 2011 and has similar inhibition constants for dopamine receptors (Larson et al, 1995). Based on in vitro studies (Klotz et al, 2010, Foote et al, 2011, it seems that ergocristine and ergovaline differ in their ability to elicit a vasoconstrictive response that is likely indicative of differences in membrane receptor binding; therefore, effects induced by ergocristine might not be representative of the potential of ergovaline to induce responses.…”