Duration of ergovaline exposure influences serotonin-mediated vasoactivity of bovine mesenteric vasculature

Authors: TROTTA, RONALD - University Of Kentucky; HARMON, DAVID - University Of Kentucky; JI, HUIHUA - University Of Kentucky; Klotz, James

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2023
Publication Date: 4/2/2023
Citation: Trotta, R.J., Harmon, D.L., Ji, H., Klotz, J.L. 2023. Duration of ergovaline exposure influences serotonin-mediated vasoactivity of bovine mesenteric vasculature. Journal of Animal Science. 100. https://doi.org/10.1093/jas/skad100.
DOI: https://doi.org/10.1093/jas/skad100

Interpretive Summary: Consumption of ergot alkaloids found in endophyte-infected tall fescue can lead to symptoms of fescue toxicosis, such as vasoconstriction, in ruminant livestock species. Ergovaline is the primary ergot alkaloid responsible for causing vasoconstriction when toxic varieties of fescue are consumed. It has been previously shown that ergovaline causes vasoconstriction by interacting with vascular serotonin receptors in cattle and sheep. Depending on when ergovaline exposure occurs, ergovaline can function as an agonist (stimulant) or antagonist (inhibitor) of vascular activity. However, it is unclear how the duration of ergovaline exposure affects vasoconstriction caused by serotonin. Experiments were conducted using the bovine mesenteric artery and mesenteric vein that were exposed to either 0, 0.01, or 0.1 uM ergovaline for 24-h prior to serotonin additions or simultaneously with serotonin additions. The results of these experiments demonstrated that the duration of ergovaline exposure influences serotonin-mediated vasoconstriction and possibly vasorelaxation in bovine mesenteric vasculature. If ergovaline and serotonin exposure occur simultaneously, ergovaline can act as an agonist or antagonist of serotonin-mediated vasoconstriction. If serotonin exposure occurs after prior ergovaline exposure, serotonin can induce vasorelaxation of blood vessels. Understanding how complex interactions between ergovaline and serotonin occur and affect vascular function will aid in the development of strategies to mitigate sustained vasoconstriction caused during fescue toxicosis. These results will be primarily of interest to other research scientists looking to better understand the mechanisms responsible for ergotism and fescue toxicosis in grazing livestock.

Technical Abstract: Ergovaline (ERV), produced in toxic endophyte-infected tall fescue, causes potent vasoconstriction of bovine peripheral and visceral vasculature. Ergovaline acts as both an agonist and an antagonist in bovine gut blood vessels through serotonin (5-HT) receptors and it appears that the type of action could be influenced by the extent of ERV exposure. Because it was unclear how the duration of ERV exposure influences 5-HT-mediated vasoactivity, experiments were designed to evaluate how simultaneous or prior ERV exposure influenced 5-HT-mediated vasoactivity of mesenteric artery (MA) and vein (MV) segments from Holstein steers (n=10). Isolated vessel segments were incubated in Krebs-Henseleit buffer containing 0, 0.01, or 0.1 uM ERV for 24-h prior to the 5-HT dose-response or exposed to fixed concentrations of 0, 0.01, or 0.1 uM ERV simultaneously during the 5-HT dose-response. Vessels were suspended in chambers of a multi-myograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and equilibrated to 1 g tension for 90 min. Vessels were exposed to increasing concentrations of 5-HT (5 × 10-8 M to 1 × 10-4 M) every 15 min and contractile responses were normalized as a percentage of the maximum contractile response induced by 120 mM KCl reference addition. Two-way analysis of variance was used to separately analyze data for each vessel type and duration of exposure using the MIXED procedure of SAS for the main effects of 5-HT and ERV concentration and the 5-HT × ERV concentration interaction. When 5-HT concentration increased from 5 × 10-8 M to 1 × 10-6 M, simultaneous addition of 0.1 uM ERV increased (P < 0.01) the contractile response of MV compared with additions of 0 uM ERV and 0.01 uM ERV. At 1 × 10-4 M 5-HT, the simultaneous presence of 0.01 uM ERV and 0.1 uM ERV decreased (P < 0.01) the contractile response of both MA and MV compared with 0 uM ERV addition. As 5-HT concentrations increased, the contractile response increased (P < 0.01) in both MA and MV with no previous ERV exposure, but decreased in MA and MV with 24-h prior exposure to 0.01 uM ERV and 0.1 uM ERV. These data demonstrate that the duration of ERV exposure influences 5-HT-mediated vasoconstriction and likely vasorelaxation in bovine mesenteric vasculature. If ERV and 5-HT exposure occur simultaneously, ERV can act as a partial agonist of 5-HT-mediated vasoconstriction. If 5-HT exposure occurs after blood vessels have had prior ERV exposure, it appears that 5-HT may induce vasorelaxation of blood vessels. More research is needed to identify receptors and mechanisms involved with 5-HT-mediated vasoconstriction and vasorelaxation before and after exposure to ERV. This will aid in the development of strategies for alleviating symptoms of sustained vasoconstriction that occur during fescue toxicosis in ruminants.