Ergot alkaloid exposure during gestation alters: II. Uterine and umbilical artery vasoactivity1.

Previous research has shown that livestock exposed to ergot alkaloids results in decreased vasoactivity of gastrointestinal and peripheral vasculature. 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 day 35 of gestation, 36 Suffolk ewes (78.24 ± 9.5 kg) were assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on day 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, and E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline ⋅ hd-1 ⋅ d-1 with E- ewes receiving the same quantity of E- seed. Gestation was terminated on day 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 (5 × 10-8 to 1 × 10-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5 × 10-9 to 1 × 10-5M; extract of tall fescue seed) in 15-min intervals. Increasing concentrations of norepinephrine generated a 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 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 responsive (P < 0.05). 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 appears protected from negative effects of ergot alkaloids; however, umbilical vasculature is not, and this could adversely influence fetal growth.

Pharmacologic assessment of bovine ruminal and mesenteric vascular serotonin receptor populations.

Prior work using a contractility bioassay determined that the serotonin (5-HT) receptor subtype 5-HT2A is present in bovine lateral saphenous veins and plays a role in ergot alkaloid (EA)-induced vascular contraction in steers grazing endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum). Ergot alkaloids have also been shown to be vasoactive in bovine gut vasculature. To determine what 5-HT receptors are involved in vasoconstriction of gut vasculature, contractility of ruminal and mesenteric arteries and veins collected from cattle was evaluated in the presence of agonists selective for 5-HT1B (CP 93129), 5-HT1D (L-694, 247), 5-HT2A (TCB-2), 5-HT2B (BW 723C86), 5-HT4 (BIMU-8), and 5-HT7 (LP 44) receptors. Segments of ruminal and mesenteric veins and arteries were collected and suspended in a multimyograph containing continuously oxygenated Krebs-Henseleit buffer. Blood vessels were exposed to increasing concentrations of 5-HT agonists every 15 min and contractile response data were normalized as a percentage of the maximum contractile response induced by 120 mM KCl. Analysis of variance was evaluated using mixed models procedure of SAS for effects of agonist concentration for each vessel type. Receptor agonists for 5-HT2B, 5-HT1D, and 5-HT7 did not induce a contractile response for ruminal or mesenteric vasculature (P > 0.05). However, when exposed to agonists for 5-HT2B or 5-HT1D, mesenteric veins relaxed below zero (P < 0.05). Exposure of all 4 blood vessel types to 5-HT2A agonist induced contractile responses (P < 0.05). The findings of this study indicate that 5-HT1D and 5-HT2B are present in mesenteric veins and may play a role in vasorelaxation. Further, 5-HT2A is present in ruminal and mesenteric vasculature, plays a role in vasoconstriction of these vessels, and could be influenced by EA exposure as has been demonstrated in peripheral blood vessels.