Lately, zinc has seen a marketing surge since zinc deficiency (ZnD) has been associated with a variety of chronic diseases. Now, a new study led by investigators at Emory University adds a new dimension to the body systems affected by ZnD. The researchers found that lower-than-normal zinc levels may contribute to high blood pressure by altering the way the kidneys handle sodium. Findings from the new study were published recently in the American Journal of Physiology-Renal Physiology through an article titled “Zinc Deficiency Induces Hypertension by Promoting Renal Sodium Reabsorption.”

“To explore the role of Zn2+ in blood pressure regulation, adult mice were fed a Zn2+ adequate (ZnA) or Zn2+ deficient (ZnD) diet, the authors wrote. “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.”

Zinc deficiency is common in people with chronic illnesses such as type 2 diabetes and chronic kidney disease. People with low zinc levels are also at a higher risk for hypertension. The way in which the kidneys either excrete sodium into the urine or reabsorb it into the body—specifically through a pathway called the sodium chloride cotransporter (NCC)—also plays a role in blood pressure control. Less sodium in the urine typically corresponds to higher blood pressure.

Recent research has suggested that zinc may help regulate proteins that in turn regulate the NCC, but a direct link between zinc-deficiency-induced hypertension has not been examined.

When the research team compared male mice with zinc deficiency to healthy controls, they found that the zinc-deficient mice developed high blood pressure and a corresponding decrease in urinary sodium excretion. Conversely, the control group did not experience the same changes. A small group of the zinc-deficient mice were fed a zinc-rich diet partway through the study. Once the animals’ zinc reached adequate levels, blood pressure began to drop and urinary sodium levels increased.

“ZnD promoted a biphasic BP response, characterized by episodes of high BP. BP increases were accompanied by reduced renal Na+ excretion and NCC upregulation,” the authors penned. “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. These data indicate that Zn2+contributes to BP regulation via modulating renal Na+ handling, renal NCC mediates ZnD-induced hypertension, and NCC is a Zn2+-regulated transporter that is upregulated with ZnD.

While the investigators were excited by their findings, they cautioned against overinterpretation of the data, as these studies are preliminary and need to be verified in human subjects.

“These significant findings demonstrate that enhanced renal [sodium] reabsorption plays a critical role in [zinc-deficiency]-induced hypertension,” the researchers concluded. “Understanding the specific mechanisms by which [zinc deficiency] contributes to [blood pressure] dysregulation may have an important effect on the treatment of hypertension in chronic disease settings.”