Actions of Quercetin, a Polyphenol, on Blood Pressure

Abstract

Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the values of various blood pressure regulatory factors, such as vascular compliance, peripheral vascular resistance, and total blood volume via anti-inflammatory and anti-oxidant actions. In addition to the anti-inflammatory and anti-oxidant actions of quercetin, we especially describe a novel mechanism of quercetin's action on the cytosolic Cl^- concentration ([Cl^-]_c) and novel roles of the cytosolic Cl^- i.e.: (1) quercetin elevates [Cl^-]_c by activating Na⁺-K⁺-2Cl^- cotransporter 1 (NKCC1) in renal epithelial cells contributing to Na⁺ reabsorption via the epithelial Na⁺ channel (ENaC); (2) the quercetin-induced elevation of [Cl^-]_c in renal epithelial cells diminishes expression of ENaC leading to a decrease in renal Na⁺ reabsorption; and (3) this reduction of ENaC-mediated Na⁺ reabsorption in renal epithelial cells drops volume-dependent elevated blood pressure. In this review, we introduce novel, unique mechanisms of quercetin's anti-hypertensive action via activation of NKCC1 in detail.

Keywords: Na+-K+-2Cl− cotransporter 1; cytosolic Cl− concentration; epithelial Na+ channel; flavonoid; quercetin.

Figure 1

Structures of quercetin (1) and its metabolites (2–5).

Figure 2

Systolic arterial pressure of Dahl salt-sensitive hypertensive rats. The systolic arterial pressure is represented as means ± SEM (n = 4 in each group). Norm: normal diet; Norm-Q: normal diet with quercetin; High: high-NaCl diet; and High-Q: high-NaCl diet with quercetin. * Significant difference between high-NaCl diet (High) and normal diet (Norm) at the same experimental time (p < 0.05). # Significant difference between high-NaCl with quercetin (High-Q) and high-NaCl diet (High) at the same experimental time (p < 0.05). Quercetin (10 mg/kg/day) was orally applied. The systolic blood pressure, which was measured under an awaking condition by the tail cuff method. Adopted from [15] with allowance for non-profit use of the figure.

Figure 3

mRNA expression of αENaC in the kidney of Dahl salt-sensitive hypertension rats. The amount of mRNA expression of αENaC is expressed as the ratio to β-actin expression. Data are represented as means ± SEM obtained from four rats. Norm: normal diet; Norm-Q: normal diet with quercetin; High: high-NaCl diet and High-Q: high-NaCl diet with quercetin. * Significant difference at the level of p < 0.05. Quercetin (10 mg/kg/day) was orally applied. Adopted from [15] with allowance for non-profit use of the figure.

Figure 4

Effect of quercetin (10 μM) on NKCC1 activity in rat pheochromocytoma PC12 cells. NKCC1 activity was estimated by measuring the bumetanide-sensitive ⁸⁶Rb uptake. Data are represented as means ± SEM. * p < 0.01 vs. DMSO. n = 3 for t = 0 min, n = 5 for t = 15 min, n = 7 for t = 30 min. This observation indicates that quercetin stimulates activity of NKCC1. Adopted from [22] with allowance for non-profit use of the figure.

Figure 5

A possible mechanism of quercetin actions on blood pressure via modification of extracellular fluid volume mediated by ENaC-mediated Na⁺ reabsorption in the kidney.