Vasoactivity and vasoconstriction changes in cattle related to time off toxic Endophyte-infected tall Fescue

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Abstract

Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture. In Experiment 1, lateral saphenous vein biopsies were conducted on 21 predominantly Angus steers (357 ± 3 kg body weight) at 0 (n = 6), 7 (n = 6), 14 (n = 5), or 28 days (n = 4) after removal from grazing pasture (3.0 ha; endpoint ergovaline + ergovalinine = 1.35 mg/kg DM) for 126 days. In Experiment 2, lateral saphenous veins were biopsied from 24 Angus-cross steers (361 ± 4 kg body weight) at 0, 21, 42, and 63 days (n = 6 per time point) following removal from grazing tall fescue pastures (3.0 ha; first 88 days endpoint ergovaline + ergovalinine = 0.15 mg/kg DM; last 18 days endpoint ergovaline + ergovalinine = 0.57 mg/kg DM) for 106 total days. Six steers (370 ± 18 kg body weight) off of bermudagrass pasture for the same time interval were also biopsied on Day 0 and Day 63 (n = 3 per time point). Additionally, in Experiment 2, cross-sectional ultrasound scans of caudal artery at the fourth coccygeal vertebra were taken on Days 0, 8, 15, 21, 29, 36, 42, and 45 to determine mean artery luminal area to evaluate vasoconstriction. In both experiments, steers were removed from pasture and housed in a dry lot and fed a corn silage diet for the duration of biopsies and ultrasound scans. Biopsied vessels used to evaluate vasoactivity were cleaned, incubated in a multimyograph, and exposed to increasing concentrations of 4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide (TCB2; 5HT2A agonist), guanfacine (GF; α2A-adrenergic agonist), and (R)-(+)-m-nitrobiphenyline oxalate (NBP; α2C-adrenergic agonist) in both experiments and ergovaline (ERV) and ergotamine (ERT) in Experiments 1 and 2, respectively. In Experiment 1, days off pasture × agonist concentration was not significant (p > 0.1) for all four compounds tested. In Experiment 2, GF, NBP, TCB2 and ERT were significant for days off pasture × agonist concentration interaction (p < 0.02) and vasoactivity increased over time. Vasoactivity to agonists was reduced (p < 0.05) when steers were initially removed from E+ tall fescue pasture compared to bermudagrass, but did not differ by Day 63 for any variable. Luminal areas of caudal arteries in steers grazed on E+ tall fescue relaxed and were similar to steers that had grazed bermudagrass for 36 days on non-toxic diet (p = 0.15). These data demonstrate changes in peripheral vasoactivity and recovery from vasoconstriction occur beyond five weeks off toxic pasture and 5HT2A receptors appear to be more dramatically affected in the lateral saphenous vein by grazing E+ tall fescue pasture than adrenergic receptors.

Figures

  • Figure 1. Serum prolactin concentrations on the day of the lateral saphenous vein biopsy relative to the number of days steers had been off of pasture consuming a non-toxic diet for: (a) Experiment 1 (effect of Day was p = 0.01); (b) Experiment 2 tall fescue steers (effect of Day was p = 0.09); and (c) Experiment 2 bermudagrass steers compared to tall fescue steers on Day 0 (effect of Pasture was p = 0.08) and Day 63 (effect of Pasture was p = 0.99). Bars not sharing the same superscripts are different (p < 0.05).
  • Table 1. Inside and outside diameters of lateral saphenous veins biopsied on Days 0, 7, 14, and 28 for Experiment 1 and on Days 0, 21, 42, and 63 for Experiment 2.
  • Figure 2. Contractile response of lateral saphenous veins (expressed as percentage of the maximal response induced by 1 × 10−4 M norepinephrine) to increasing concentrations of: (a) ergovaline in Experiment 1 at 0, 7, 14, and 28 days (−logEC50 = 4.46, 5.06, 4.85, and 4.50, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day × ergovaline concentration interaction was not significant (p = 0.66)); and (b) ergotamine in Experiment 2 at 0, 21, 42, and 63 days (−logEC50 = 4.89, 4.98, 5.09, and 5.18, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x ergotamine concentration interaction was significant (p < 0.01)). Comparison of contractile responses of lateral saphenous veins biopsied from steers that had grazed toxic tall fescue (red lines) and non-toxic bermudagrass (black lines) pastures at (c) 0 and (d) 63 days after removal from pasture in Experiment 2.
  • Figure 3. Contractile response of lateral saphenous veins (expressed as percentage of the maximal response induced by 1 × 10−4 M norepinephrine) to increasing concentrations of guanfacine HCl, an α2A-adrenergic receptor agonist in: (a) Experiment 1 on Days 0, 7, 14, and 28 (−logEC50 = 5.75, 5.05, 5.19, and 4.73, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x guanfacine concentration interaction was significant (p < 0.01)); and (b) Experiment 2 on Days 0, 21, 42, and 63 (−logEC50 = 4.69, 4.91, 4.88, and 5.33, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x guanfacine concentration interaction was significant (p < 0.01)). Comparison of contractile responses of lateral saphenous veins biopsied from steers that had grazed toxic tall fescue (red lines) and non-toxic bermudagrass (black lines) pastures at (c) 0 and (d) 63 days after removal from pasture in Experiment 2.
  • Figure 4. Contractile response of lateral saphenous veins (expressed as percentage of the maximal response induced by 1 × 10−4 M norepinephrine) to increasing concentrations of nitrobiphenyline oxalate (NBP), an α2C-adrenergic receptor agonist in: (a) Experiment 1 on Days 0, 7, 14, and 28 (−logEC50 = 4.91, 5.23, 5.19, and 4.99, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x NBP concentration interaction was not significant (p = 0.41)); and (b) Experiment 2 on Days 0, 21, 42, and 63 (−logEC50 = 4.87, 5.05, 4.95, and 5.17, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x NBP concentration interaction was significant (p = 0.017)). Comparison of contractile responses of lateral saphenous veins biopsied from steers that had grazed toxic tall fescue (red lines) and non-toxic bermudagrass (black lines) pastures at (c) 0 and (d) 63 days after removal from pasture in Experiment 2.
  • Figure 5. Contractile response of lateral saphenous veins (expressed as percentage of the maximal response induced by 1 × 10−4 M norepinephrine) to increasing concentrations of TCB2, an 5-hydroxytryptamine2A receptor agonist in: (a) Experiment 1 on Days 0, 7, 14, and 28 (−logEC50 = 4.71, 4.92, 4.76, and 4.65, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x TCB2 concentration interaction was not significant (p = 0.39)); and (b) Experiment 2 on Days 0, 21, 42, and 63 (−logEC50 = 4.67, 4.64, 4.75, and 5.02, respectively) after steers were removed from a tall fescue pasture and placed on a non-toxic diet (day x TCB2 concentration interaction was significant (p < 0.01)). Comparison of contractile responses of lateral saphenous veins biopsied from steers that had grazed toxic tall fescue (red lines) and non-toxic bermudagrass (black lines) pastures at (c) 0 and (d) 63 days after removal from pasture in Experiment 2.
  • Figure 6. Doppler ultrasound measures of the change in luminal area of caudal arteries of steers that had been removed from either a toxic tall fescue or a non-toxic bermudagrass pasture. Luminal areas were regressed over days on a non-toxic diet relative to removal from pasture.

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Klotz, J. L., Aiken, G. E., Bussard, J. R., Foote, A. P., Harmon, D. L., Goff, B. M., … Strickland, J. R. (2016). Vasoactivity and vasoconstriction changes in cattle related to time off toxic Endophyte-infected tall Fescue. Toxins, 8(10). https://doi.org/10.3390/toxins8100271

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