Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol, relax arteries ex vivo and decrease blood pressure in vivo

Vascul Pharmacol. 2018 Dec;111:36-43. doi: 10.1016/j.vph.2018.08.008. Epub 2018 Aug 15.


Scope: The flavonoid quercetin reduces arterial blood pressure in animals and humans but the mechanisms remains elusive. The aim of this study was to test the activity of flavonoid microbial metabolites, which can participate on the final vasorelaxant effect.

Methods and results: Both ex vivo (isolated rat thoracic aorta and mesenteric artery) and in vivo (normotensive and spontaneously hypertensive rats) approaches were used in this study. 4-methylcatechol and 3,4-dihydroxyphenylacetic acid (DHPA) had greater vasorelaxant effects on mesenteric artery than 3-(3-hydroxyphenyl)propionic acid, the previously reported metabolite with vasorelaxant effect. In vivo testing confirmed their blood pressure decreasing effect given both as bolus and slow infusion. Their mechanism at molecular level was different.

Conclusions: This study is the first to show that flavonoid metabolites DHPA and 4-methylcatechol decrease arterial blood pressure and hence a mixture of microbial metabolites formed in the gastrointestinal tract may be responsible for or contribute to the effect of orally ingested quercetin.

Keywords: Blood pressure; Flavonoid; Metabolite; Phenolic; Vascular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Aorta, Thoracic / drug effects*
  • Arterial Pressure / drug effects*
  • Catechols / pharmacology*
  • Disease Models, Animal
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries / drug effects*
  • Rats, Inbred SHR
  • Rats, Wistar
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*


  • Antihypertensive Agents
  • Catechols
  • Vasodilator Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • 4-methylcatechol