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.
Highlights
Almost half of the adult population in the United States have high blood pressure, defined as a systolic blood pressure (SBP) ≥ 130 mm Hg or a diastolic blood pressure (DBP) ≥ 80 mm Hg, or as taking medication for hypertension [1]
Evidence from numerous studies indicates that cytochrome P450 (CYP)-mediated metabolism of arachidonic acid (AA) in the kidney generates vasoactive metabolites that play a key role in the regulation of vascular tone and blood pressure [2,3,4,5]
This study has shown that sub-chronic administration of QR reduces blood pressure in young
Summary
Almost half of the adult population in the United States have high blood pressure, defined as a systolic blood pressure (SBP) ≥ 130 mm Hg or a diastolic blood pressure (DBP) ≥ 80 mm Hg, or as taking medication for hypertension [1]. Due to several socio-economic and pathological reasons, only 24% of patients with hypertension have their blood pressure under control [1]. Regulation of blood pressure is maintained through several integrated cardiac, vascular, neuronal, and hormonal factors. Evidence from numerous studies indicates that cytochrome P450 (CYP)-mediated metabolism of arachidonic acid (AA) in the kidney generates vasoactive metabolites that play a key role in the regulation of vascular tone and blood pressure [2,3,4,5]. The AA metabolites that have been extensively studied and demonstrated a significant role in blood pressure regulation are hydroxyeicosatetraenoic acids (HETEs; 19- and 20-HETE) and epoxyeicosatetraenoic acids (EETs, Figure 1) [6]. 2020, 21, 6554; doi:10.3390/ijms21186554 www.mdpi.com/journal/ijms and thymoquinone on drug‐metabolizing enzymes and blood pressure [6,18,19]. We applied a similar approach to the natural phytochemical quercetin (QR), which is one of the most abundant flavonoids with a wide variety of therapeutic benefits including cardioprotection and anti‐
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