PSVII-33 Determination of serotonergic receptor profiles in equine palmar artery and vein and uterine artery

Abstract

Abstract Ergot alkaloids are secondary metabolites produced by the fungal endophyte (Epichloë coenophiala) found in tall fescue (Lolium arundinaceum). Previous research has demonstrated that ergot alkaloids are vasoactive in equine palmar artery and vein but less in uterine artery. Work in cattle has shown that ergot alkaloids interact with serotonin receptors causing prolonged vasoconstriction associated with fescue toxicosis. The objective of this study was to pharmacologically assess vasoactivity of equine palmar artery and vein and uterine artery using selective agonists for serotonin receptor subtypes 5HT1B, 1D, 2A, 2B, and 7. Following euthanasia, palmar arteries, veins and uterine arteries were collected from 6 mixed breed mares. Blood vessels were separated, cleaned of external connective and adipose tissue, divided into 2–3 mm cross-sections and suspended in multi-myograph chambers containing continuously oxygenated Krebs-Henseleit buffer (95%O2/5%CO2; pH=7.4; 37°C). Following a 90-min equilibration of vascular tension and recovery from a reference addition of 1x10-4 M norepinephrine, increasing concentrations of agonists CP 93129 dihydrochloride (5HT1B), PNU 142633 (5HT1D), and TCB-2 (5HT2A) were added in 15-min intervals to assess to role of these receptors in vasoconstriction. Agonists BW 723C86 (5HT2B) and LP 44 (5HT7) were added to blood vessels precontracted with 1x10-4 M ergonovine to assess these receptors and vasorelaxation. Data were normalized as percent contractile response induced by the reference additions and analyzed as a completely randomized design using SAS. The agonists for 5HT1B and 1D did not induce a contractile response in any blood vessels tested (P > 0.05). The agonist for 5HT2A induced contractile response in all vessels tested (P < 0.05). The agonists for 5HT2B and 7 did not induce vasorelaxation different from ergonovine control (only vehicle additions) (P > 0.05). These results indicate that future work with ergot alkaloid induced vasoconstriction in equine vasculature should target the 5HT2A receptor.