Zinc deficiency could exacerbate hypertension

Researchers from Wright State University in Ohio have identified a new culprit behind uncontrolled high blood pressure (BP): zinc.

Zinc deficiency (ZnD) is common in individuals with type 2 diabetes, chronic kidney disease and a handful of other chronic conditions, lead author Clintoria R. Williams, PhD, and colleagues wrote in the American Journal of Physiology: Renal Physiology on Jan. 16. In those patients, ZnD exacerbates an already increased likelihood of hypertension.

“In support of ZnD contributing to BP dysregulation, populations with low dietary zinc intake have a high prevalence of hypertension,” Williams and co-authors wrote. “Collectively, these and other epidemiological studies suggest a possible inverse correlation between zinc levels and BP.”

The authors said renal modulation of urinary sodium excretion is the “cornerstone” of blood pressure regulation, and the way kidneys either excrete sodium into the urine or reabsorb it into the body is dictated by the sodium chloride cotransporter (NCC) pathway—a pathway that’s also implicated in genetic disorders of hypo- and hypertension. Hypothesizing zinc might regulate proteins that in turn regulate the NCC, Williams et al. undertook a study of mice who were fed either a zinc-adequate (ZnA) or zinc-deficient (ZnD) diet, tracking sodium and zinc levels in relation to BP.

Partway through the study, a subset of ZnD mice were either returned to a ZnA diet or administered hydrochlorothiazide (HCTZ), an NCC inhibitor. The researchers conducted both in vivo and in vitro analyses.

According to results, ZnD promoted a biphasic response in the mice that was characterized by episodes of hypertension. BP increases were accompanied by reduced renal sodium excretion and NCC upregulation—effects that were reversed in ZnA mice—and HCTZ appeared to stimulate natriuresis and reverse BP outcomes.

The authors said their findings suggest zinc contributes to BP regulation by modulating renal sodium transport, and renal NCC seems to mediate ZnD-induced hypertension.

“Although our novel results do indicate that zinc plays a critical role in NCC regulation, the specific mechanisms involved are unknown,” they wrote. “Collectively, our findings suggest that transcriptional and post-translational mechanisms may be involved. For example, zinc is an essential cofactor of transcription factors involved in BP regulation.”

Williams et al. said their trial also reveals NCC is a zinc-regulated transporter which is upregulated with ZnD, linking dysregulated renal sodium to ZnD-induced hypertension.

“This study is the first to link dysregulated renal sodium transport to ZnD-induced hypertension,” the authors wrote. “Furthermore, NCC represents a novel mechanism by which zinc regulates BP. Understanding the specific mechanisms by which ZnD contributes to BP dysregulation may have an important impact on the treatment of hypertension in chronic disease settings.”