Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature.
James L KlotzJessica L BrittMaslyn A GreeneCoral Kent-DennisSusan K DuckettPublished in: Human & experimental toxicology (2024)
Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT 2A and 5-HT 1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT 1B/1D agonist and 5-HT 2A agonist. The 5-HT 1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT 2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased ( p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes ( p < 0.05). Veins responded to increasing concentrations of the 5-HT 2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT 2A agonist ( p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON ( p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT 2A receptor activity and not 5-HT 1B/1D . Umbilical artery 5-HT 2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.