|Xue, Y -|
|Matthews, James -|
|Boling, James -|
|Burris, W -|
|Bush, Lowell -|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 7, 2011
Publication Date: February 1, 2012
Citation: Klotz, J.L., Brown, K.R., Xue, Y., Matthews, J.C., Boling, J.A., Burris, W.R., Bush, L.P., Strickland, J.R. 2012. Alterations in serotonin receptor-induced contractility of bovine lateral saphenous vein in cattle grazing endophyte-infected tall fescue. Journal of Animal Science. 90:682-693. Interpretive Summary: Many symptoms of the tall fescue toxicosis syndrome have been related to impaired peripheral circulation. Ergot alkaloids produced by the tall fescue Lolium arundinaceum - endophyte Neotyphodium coenophialum symbiont have a negative effect on vascular circulation by damaging the endothelial lining, narrowing vessel lumens, and ultimately, reduce blood flow that can result in tissue necrosis. The objectives of this study were to further characterize contractile responses through different serotonin (5HT) receptors, determine if these responses are altered by grazing either high or low endophyte-infected tall fescue, and to determine if responses are altered by consumption of endophyte-free feedstuffs after initial consumption of endophyte-infected tall fescue Taken together, the results of Experiments 1 and 2 demonstrated induction of fescue toxicosis in the HE exposed steers and this chronic exposure to ergot alkaloids through grazing endophyte-infected tall fescue affects bovine vasculature at the receptor level. Specifically, the 5HT2A and 5HT7 receptors are affected, although differently. These receptors are likely involved in some aspect of the vasoconstriction related to many symptoms of fescue toxicosis. Although, there may be other biogenic amine receptors involved in fescue toxicosis-associated vasoconstriction, 5HT2A appears to play a dominant role in conveying the vasoconstrictive effects of the ergot alkaloids. These effects of endophyte level, however, appear to be ameliorated by the finishing period prior to slaughter. This indicates that the effects of the involved ergot alkaloids are reversible.
Technical Abstract: As part of a large 2-year study documenting the physiologic impact of grazing endophyte-infected tall fescue on growing cattle, 2 experiments were conducted to characterize and evaluate the effects of grazing 2 levels of toxic endophyte-infected tall fescue pastures on vascular contractility and serotonin receptors. Experiment 1 examined the vasoconstrictive activities of 5-hydroxytryptamine (5HT), '-methylserotonin (ME5HT; a 5HT2 receptor agonist), D-lysergic acid (LSA), and ergovaline (ERV) on lateral saphenous veins collected from steers immediately removed from either a high endophyte-infected tall fescue pasture (HE) or a low endophyte-infected mixed grass (LE) pasture. The following year, using the same pastures, Experiment 2 evaluated the effect of grazing 2 levels of toxic endophyte-infected tall fescue on the vasoconstrictive activities of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), BW 723C86 (BW7), CGS-12066A (CGS), and 5-carboxamidotryptamine hemiethanolate maleate (5CT), agonists for 5-hydroxytryptamine (5HT)2A, 2B, 5HT1B and 5HT7 receptors, respectively. Half of the steers in Experiment 2 were slaughtered immediately after removal from pasture and the other half were fed finishing diets (finished) for > 91 d prior to slaughter. For Experiment 1, maximal contractile intensities (1 ' 10-4 M) were greater (P<0.05) for steers grazing LE pastures than HE pastures for 5HT (73.3 vs 48.9 '2.1%), ME5HT (52.7 vs 24.9 '1.5%), and ERV (65.7 vs 49.1 '2.6%). Onset of contractile response did not differ for 5HT and ERV, but onset of ME5HT contraction was not initiated (P < 0.05) in HE steers until 10-4 compared to 10-5 M in LE grazing steers. For Experiment 2, maximal contractile intensities achieved with DOI were 35% lower (P < 0.05), whereas those achieved with 5CT were 37% greater (P < 0.05), in steers grazing HE pastures. The contractile response to CGS did not differ between pasture groups and there was an absence of contractile response to BW7 in both groups. There were no differences between endophyte levels in contractile responses after animals were finished for > 91 d. Results from Experiment 1 demonstrate that grazing of HE pastures for 89-105 d induces functional alterations in blood vessels, as evidenced by reduced contractile capacity and altered serotonergic receptor activity. Results from Experiment 2 demonstrated that grazing HE pastures alters vascular responses, which may be mediated through altered serotonin receptor activities and that these alterations may be ameliorated by removal of ergot alkaloid exposure as demonstrated by the absence of differences in the finished steers.