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

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 dosedependent contraction at concentrations ranging from 10 to 100 mM on human umbilical artery rings. TMA-induced contractions were more potent than TMAOinduced contractions (TMA: ÀlogEC50 = 1.00 ± 0.02, TMAO: ÀlogEC50 = 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 Ca 2+ and calcium influx through L-type Ca 2+ 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. K E Y W O R D S human umbilical artery, isolated organ bath, trimethylamine, trimethylamine-n-oxide, vascular diseases