Abstract

In the present study, we aimed to investigate the preventive effects of 4-hydroxychalcone (4HCH) on resistant hypertension. We used cryptochrome-null mice, which characteristically show high plasma aldosterone levels, inflammation, and renal injury. The cryptochrome-null mice received high-salt treatment and were treated orally with 4HCH 10 mg/kg, 4HCH 20 mg/kg, and 4HCH 40 mg/kg, respectively. The salt administration in cryptochrome-null mice is able to induce an increase in systolic pressure which is associated with hyperaldosteronism, inflammation, and kidney injury. Treatment with 40 mg/kg 4HCH reduced systolic hypertension, serum IL-1β, and TNF-α levels and suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and renal injury. The impact of 4HCH on the hyperaldosteronism, inflammation, and kidney injury provides new insights for future development of therapeutic strategies in resistant hypertension.

Highlights

  • Resistant hypertension (RH) refers broadly to high blood pressure that is resistant to pharmacologic therapy

  • We present for the first time the evidence that 4HCH inhibits RH by attenuating hyperaldosteronism, inflammation, and renal injury in cryptochrome-null mice (CNM)

  • CNM have elevated blood pressure compared with their WT littermate controls (Figure 1)

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Summary

Introduction

Resistant hypertension (RH) refers broadly to high blood pressure that is resistant to pharmacologic therapy. Chalcones (1,3-diaryl-2-propen-1-ones) belong to the largest class of plant secondary metabolites and are considered to be precursors of flavonoids and isoflavonoids serving in plant defense mechanisms to counteract reactive oxygen species in order to survive and prevent molecular damage and damage by microorganisms, insects, and animals [6]. Chalcones and their derivatives exerted a lot of biological properties [7, 8], but few previous reports referred to the ability of these classes of compounds to lower blood pressure via the blockade of aldosterone. We present for the first time the evidence that 4HCH inhibits RH by attenuating hyperaldosteronism, inflammation, and renal injury in cryptochrome-null mice (CNM)

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