285 Duration of Ergovaline Exposure Influences Serotonin-Mediated Vasoconstriction and Vasorelaxation of Bovine Vasculature

Abstract

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 mM ERV for 24-h befoe the 5-HT dose-response or exposed to fixed concentrations of 0, 0.01, or 0.1 mM 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 mM ERV increased (P < 0.01) the contractile response of MV compared with additions of 0 mM ERV and 0.01 mM ERV. At 1 ′ 10-4 M 5-HT, the simultaneous presence of 0.01 mM ERV and 0.1 mM ERV decreased (P < 0.01) the contractile response of both MA and MV compared with 0 mM 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 mM ERV and 0.1 mM 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.