Effects of Ergot Alkaloid Exposure during Gestation on Maternal and Fetal Vasoactivity in Sheep.

Previous research has shown that exposure to ergot alkaloids found in endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) results in decreased vasoactivity. Little is known regarding the effect ergot alkaloid exposure during gestation may have on vasculature supporting the fetus. The objective of this study was to evaluate contractile responses of uterine and umbilical arteries collected from ewes consuming ergot alkaloids during gestation. On d 35 of gestation, 36 Suffolk ewes (78.24 ±9.5 kg) were randomly assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on d 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline/head/d with E- ewes receiving the same quantity of E- seed. Gestation was terminated on d 133, and sections of uterine artery and umbilical cord were surgically collected. Only collections from 28 ewes (n=7/treatment) were of sufficient viability to proceed with the contractility experiments. Arteries were cleaned, sliced into 2-mm cross sections, and suspended in multi-myograph chambers containing 5 mL of continuously oxygenated Krebs-Henseleit buffer. Vessels were exposed to increasing concentrations (5x10^-8 to 1x10^-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5x10^-9 to 1x10^-5 M; extract of tall fescue seed) in 15-min intervals. Data were normalized as a percentage of the maximum contractile response induced by a reference dose of 120 mM KCl. Data from each artery were analyzed using mixed models of SAS as a split-plot with seed and myograph treatments as the whole and sub-plot treatments, respectively. Increasing concentrations of norepinephrine generated a moderate contractile response by the uterine artery (P< 0.05), but no response in the umbilical artery. Increasing concentrations of serotonin resulted in negligible responses in uterine preparations, whereas umbilical artery preparations were very responsive (P<0.05) to serotonin. Ewes receiving E+E+ and E-E+ treatments had decreased vasoactivity in umbilical arteries to serotonin with a dextral shift in concentrations where the response curve initiated (P< 0.05). Interestingly, uterine arteries were not responsive to exposure to ergotamine or ergovaline, whereas umbilical arteries were very responsive. Umbilical arteries collected from ewes receiving E-E- and E+E- were more vasoactive to ergot alkaloids (P<0.05) than other treatments. These findings indicate that maternal blood supply to the placenta is protected from negative effects of ergot alkaloids; however, umbilical vasculature is not and this could negatively affect fetal growth.