The Antihypertensive Effect of Quercetin in Young Spontaneously Hypertensive Rats; Role of Arachidonic Acid Metabolism

Int J Mol Sci. 2020 Sep 8;21(18):6554. doi: 10.3390/ijms21186554.

Abstract

Hypertension affects almost 50% of the adult American population. Metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the blood pressure-lowering potential of quercetin (QR), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered QR in drinking water at concentrations of 10, 30, and 60 mg/L. Blood pressure was monitored at seven-day intervals. After a total of seven weeks of treatment, rats were killed and kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Medium- and high-dose QR resisted the rise in blood pressure observed in the untreated SHR and significantly inhibited the activity of the CYP4A enzyme in renal cortical microsomes. The activity of the sEH enzyme in renal cortical cytosols was significantly inhibited only by the high QR dose. Our data not only demonstrate the antihypertensive effect of QR, but also provide a novel mechanism for its underlying cardioprotective properties.

Keywords: 20-HETE; EETs; arachidonic acid; hypertension; metabolism; quercetin; soluble epoxide hydrolase; spontaneously hypertensive rats.

MeSH terms

  • Animals
  • Antihypertensive Agents / metabolism
  • Antihypertensive Agents / pharmacology
  • Arachidonic Acid / metabolism*
  • Arachidonic Acid / physiology
  • Blood Pressure / drug effects
  • Cytochrome P-450 CYP4A / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Epoxide Hydrolases / metabolism
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Hypertension / drug therapy
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Kidney / metabolism
  • Kidney Cortex / metabolism
  • Male
  • Microsomes / metabolism
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Rats
  • Rats, Inbred SHR

Substances

  • Antihypertensive Agents
  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • Cytochrome P-450 Enzyme System
  • Quercetin
  • Cytochrome P-450 CYP4A
  • Epoxide Hydrolases