Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature

Authors: Klotz, James; DUCKETT, SUSAN - CLEMSON UNIVERSITY; BRITT, JESSSI - CLEMSON UNIVERSITY; GREENE, MASLYN - CLEMSON UNIVERSITY; ANDRAE, JOHN - CLEMSON UNIVERSITY

Submitted to: Journal of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: 4/22/2022
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Consumption of ergot alkaloids during the second half of gestation have been shown to decrease umbilical artery vasoactivity resulting in lower birth weights. The negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors. The objective was to evaluate the vasoactivity of serotonin (5HT) receptors 5HT2A and 5HT1B/1D in the umbilical artery and vein from ewes receiving endophyte-infected (E+ 1.77 mg ergovaline/hd/d) or endophyte-free (E-; 0 mg ergovaline/hd/d) 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. Gravid reproduction tracts were collected from ewes at slaughter. The umbilical cord from the first exteriorized fetus was ligated and placed in Krebs-Henseleit buffer. Umbilical arteries and veins were cleaned of excess adipose and connective tissue and stored in Krebs-Henseleit buffer at 4' C until initiation of myograph experiments the following day. Two mm cross sections of each blood vessel were luminally mounted in multi-myographs containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and exposed to a reference dose of 120 mM KCL followed by increasing concentrations of rizatriptan benzoate (5HT1B/1D agonist) and TCB-2 (5HT2A agonist) that ranged from 5 x 10-9 M to 1 x 10-4 M. The 5HT1B/1D agonist did not stimulate a contractile response in either the umbilical artery or vein for any gestation time point evaluated. The 5HT2A agonist caused large contractile responses in the 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 ewe receiving the E+ treatment (P < 0.05). The umbilical vein also responded to increasing concentrations of the 5HT2A agonist. The maximal response of the umbilical vein was not different between d 85 and 110 of gestation, but both were greater than d 133 when exposed to 5HT2A agonist. 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 the vascular smooth muscle contractions of the umbilical artery and vein are induced by 5HT2A receptor activity and not 5HT1B/1D. Umbilical artery 5HT2A receptor activity responded to seed treatment differently than umbilical vein and could be the source of ergot alkaloid-induced intra-uterine growth restriction observed when ewes graze toxic tall fescue during gestation.