Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension

Curr Med Chem. 2019;26(1):232-243. doi: 10.2174/0929867324666171006122656.


Background: Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood.

Objective: The main goal of this pilot study was to determine and compare plasma metabolomic profiles in resistant and non-resistant hypertensive patients.

Methods: We applied untargeted metabolomic profiling in plasma samples collected from 69 subjects with RH and 81 subjects with controlled hypertension. To confirm patients' compliance to antihypertensive treatment, levels of selected drugs and their metabolites were determined in plasma samples with the LC-ESI-TOF/MS technique.

Results: The results showed no statistically significant differences in the administration of antihypertensive drug in the compared groups. We identified 19 up-regulated and 13 downregulated metabolites in the RH.

Conclusion: The metabolites altered in RH are linked to oxidative stress and inflammation, endothelium dysfunction, vasoconstriction and cell proliferation. Our results may generate new hypothesis about RH development and progression.

Keywords: Resistant hypertension; biomarker candidates; liquid chromatography; mass spectrometry; metabolomics; multivariate analysis..

MeSH terms

  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / therapeutic use*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Hypertension / metabolism*
  • Male
  • Metabolomics*
  • Middle Aged
  • Multivariate Analysis
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry


  • Antihypertensive Agents