296 - Ergot Alkaloid Consumption Alters Serotonin Receptor-induced Vasoactivity in Ovine Umbilical Vasculature

Abstract: Consumption of ergot alkaloids during the second half of gestation have been shown to decrease umbilical artery vasoactivity resulting in lighter birth weights. The objective was to evaluate vasoactivity of serotonin (5HT) receptors 5HT_2A and 5HT_1B/1D in umbilical artery and vein from ewes receiving endophyte-infected (E+ 1.77 mg ergovaline/animal/day) or endophyte-free (E-; 0 mg ergovaline/animal/day) tall fescue seed at d-85 (n=4), 110 (n=4 E+; n=4 E-), 135 (n =4 E+; n=4 E-) of gestation. Suffolk ewes began receiving seed treatments on d-86 of gestation. Umbilical artery and vein were collected from ewes at slaughter. Two-mm blood vessel cross sections were mounted in multi-myographs containing Krebs-Henseleit buffer and exposed to increasing concentrations of rizatriptan benzoate (5HT_1B/1D agonist) and TCB-2 (5HT_2A agonist). Data were analyzed as a split-plot with mixed models of SAS. The 5HT_1B/1D agonist did not stimulate a contractile response in either vessel for any gestation time point evaluated. The 5HT_2A agonist caused contractile responses in umbilical artery with the greatest occurring at d-85 and decreasing in magnitude as days of gestation increased (P< 0.05). On d-110 and 133 of gestation, umbilical arteries from ewes receiving E- seed had a greater contractile response than those arteries collected from ewes receiving the E+ treatment (P< 0.05). Umbilical veins also responded to increasing concentrations of 5HT_2A agonist and maximal response was not different between d-85 and 110 of gestation, but both were greater than d-133. Unlike the artery, umbilical veins from ewes receiving E+ seed had greater contractile response than E- at d-133 (P< 0.05). These results demonstrate that ovine vascular smooth muscle contractions of the umbilical artery and vein are induced by 5HT_2A receptor activity and not 5HT_1B/1D. Umbilical artery 5HT_2A receptor activity responded to seed treatment differently than umbilical vein and could be the source of ergot alkaloid-induced intra-uterine growth restriction.