Zinc Deficiency Plays a Role in High Blood Pressure

• Post by: clintoriaw
• January 23, 2019
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Zinc Deficiency Induces Hypertension by Promoting Renal Na⁺ Reabsorption

Clintoria R. Williams, Monisha Mistry, Aswathy M. Cheriyan, Jasmine M. Williams, Meagan K. Naraine, Carla L. Ellis, Rickta Mallick, Abinash C. Mistry, Jennifer L. Gooch, Benjamin Ko, Hui Cai and Robert S. Hoover

Zn²⁺ deficiency (ZnD) is a common comorbidity of many chronic diseases. In these settings, ZnD exacerbates hypertension. Whether ZnD alone is sufficient to alter blood pressure (BP) is unknown.

Study’s Objective: To explore the role of Zn²⁺ in BP regulation, adult mice were fed a Zn²⁺ adequate (ZnA) or Zn²⁺ deficient (ZnD) diet. 

Experimental Design: A subset of ZnD mice were either returned to a ZnA diet or administered hydrochlorothiazide (HCTZ), a sodium chloride cotransporter (NCC) inhibitor. To reduce intracellular Zn²⁺in vitro, mouse distal convoluted tubule cells were cultured in TPEN (Zn²⁺ chelator)- or vehicle (DMSO)-containing medium. To replete intracellular Zn²⁺, TPEN-exposed cells were then cultured in Zn²⁺-supplemented medium.

Major Findings: Results show that ZnD promoted a biphasic BP response, characterized by episodes of high BP. BP increases were accompanied by reduced renal Na⁺ excretion and NCC upregulation. These effects were reversed in Zn²⁺-repleted mice. Likewise, HCTZ stimulated natriuresis and reversed BP increases. In vitro, Zn²⁺ depletion increased NCC expression. Furthermore, TPEN promoted NCC surface localization and Na⁺ uptake activity. Zn²⁺ repletion reversed TPEN effects on NCC.

Conclusions: These data indicate that:

1. Zn²⁺ contributes to BP regulation via modulating renal Na⁺ transport,
2. renal NCC mediates ZnD-induced hypertension and
3. NCC is a Zn²⁺-regulated transporter that is upregulated with ZnD.

Significance: This study links dysregulated renal Na⁺ handling to ZnD-induced hypertension. Furthermore, NCC is identified as a novel mechanism by which Zn²⁺ regulates BP. Understanding the mechanisms of ZnD-induced BP dysregulation may have important therapeutic impact on hypertension.

Click the link to read the full article: https://www.physiology.org/doi/abs/10.1152/ajprenal.00487.2018