Contractile effect of trimethylamine and trimethylamine-n-oxide on isolated human umbilical arteries

J Obstet Gynaecol Res. 2023 Jul;49(7):1736-1742. doi: 10.1111/jog.15656. Epub 2023 Apr 12.

Abstract

Background: The aim of this study is to investigate the effect of trimethylamine (TMA) and trimethylamine-n-oxide (TMAO) on the contractility of human umbilical artery and the possible mechanisms involved.

Methods: Vasoactive responses to TMA and TMAO on human umbilical artery rings were measured in isolated organ baths. Cumulative dose-response curves for TMA and TMAO were obtained before and after incubation with atropine, yohimbine, prazosin, indomethacin, verapamil, and Ca+2 -free Krebs-Henselite solution.

Results: Administration of cumulative TMA and TMAO resulted in dose-dependent contraction at concentrations ranging from 10 to 100 mM on human umbilical artery rings. TMA-induced contractions were more potent than TMAO-induced contractions (TMA: -logEC50 = 1.00 ± 0.02, TMAO: -logEC50 = 0.57 ± 0.02). Contraction responses to TMA were significantly lower in the presence of verapamil and in the absence of external Ca+2 (p < 0.001, p < 0.05, respectively).

Conclusion: Our results showed that TMA and TMAO caused vasoconstriction in isolated human umbilical artery rings. Our findings also indicated that TMA but not TMAO-induced vasoconstriction was partially dependent on extracellular Ca2+ and calcium influx through L-type Ca2+ channels. Our results suggest that TMA and TMAO may have the potential to contribute to cardiovascular diseases through their direct effect on vascular contractility in human arteries.

Keywords: human umbilical artery; isolated organ bath; trimethylamine; trimethylamine-n-oxide; vascular diseases.

MeSH terms

  • Humans
  • Methylamines* / administration & dosage
  • Methylamines* / pharmacology
  • Oxides
  • Umbilical Arteries* / drug effects

Substances

  • Methylamines
  • Oxides
  • trimethylamine
  • trimethyloxamine