Potassium2026-06

Neuraminidase1 Activity Contributes to Vasopressin Receptor-mediated Augmentation of Water and Electrolyte Retention by the Kidney in Haploinsufficient Mice.

Kaur Gagandeep, Serwaa-Bonsu Akua, Miyasako Kisho, McCormick James A et al. — bioRxiv : the preprint server for biology

Summary

This study in mice explores how a specific enzyme, neuraminidase-1, affects the kidneys' ability to retain water and electrolytes, particularly in a genetic condition similar to Williams syndrome. Researchers found that this enzyme plays a role in how the kidneys respond to a hormone called vasopressin, influencing how much water and salt are kept in the body. Understanding this mechanism could offer new insights into kidney dysfunction and high blood pressure.

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Key points

This mouse study investigated how a specific enzyme impacts kidney function in a genetic condition.
The enzyme, neuraminidase-1, influences how kidneys manage water and electrolytes like sodium.
It affects the kidneys' response to vasopressin, a hormone that regulates body fluid balance.
These findings could help explain certain types of kidney problems and high blood pressure.

What the study looked at

What question did the study ask? This research aimed to understand how a specific enzyme called neuraminidase-1 (NEU1) contributes to the kidneys' abnormal handling of water and electrolytes in mice with a genetic condition similar to Williams syndrome. This condition, caused by a partial deletion of the elastin gene, often leads to high blood pressure and kidney issues, but the exact mechanisms are not fully understood. How was it studied? Scientists used male and female mice that had only one copy of the elastin gene, mimicking the human condition, and compared them to normal mice. They gave the mice extra fluid and then used various medications to block or stimulate specific pathways in the kidneys, including those involving the hormone vasopressin and the NEU1 enzyme. They then measured how much urine the mice produced and how much sodium was excreted. What did it find? The study found that in mice with the genetic condition, NEU1 activity plays a significant role in how their kidneys retain water and sodium, especially in response to vasopressin. Specifically, blocking NEU1 activity helped increase urine flow and sodium excretion in these mice. The effects were also observed to differ between male and female mice, suggesting sex-specific mechanisms. These findings suggest that NEU1 may be a key player in the kidney dysfunction seen in this genetic disorder.

Dietary takeaway

While this study focuses on a specific genetic condition and the role of an enzyme in kidney function, it highlights the complex interplay of electrolytes like sodium and potassium in maintaining fluid balance. Maintaining a balanced intake of potassium-rich foods, such as fruits, vegetables, and legumes, alongside managing sodium intake, is generally beneficial for kidney health and blood pressure. However, it's important to remember that this research was conducted in mice and focused on a specific genetic disorder; these findings alone do not provide direct dietary recommendations for the general public and require further human studies.

Abstract

UNLABELLED: Elastin haploinsufficiency is a primary determinant of arteriopathy and hypertension that hallmark Williams syndrome (WS), a rare genetic disorder resulting from microdeletion of genes on human chromosome 7, including the elastin gene ( ). Accumulating evidence suggests renal dysfunction, including enhanced sodium and water retention as an underlying cause of blood pressure elevation resulting from heterozygous deletion of ( ) in mice that recapitulates the cardiovascular phenotype of WS. However, the underlying pathophysiological mechanisms are poorly understood. Here, we determined whether the activity of neuraminidase-1 (NEU1) of the elastin receptor complex (ERC) contributes to abnormal handling of water and electrolytes by the kidney in haploinsufficiency. Adult male and female and mice were subjected to acute extracellular fluid volume expansion with normal saline, combined with pharmacological intervention targeting vasopressin V2 receptor (V2R), NEU1, ENaC, and NKCC2. In male mice, V2R blockade induced a dose-dependent increase in urine flow rate without affecting sodium excretion. Conversely, V2R stimulation with desmopressin markedly increased urinary sodium excretion in male but not mice, while both sexes of mice exhibited marked suppression of urine flow rate. Abrogation of ERC signaling through NEU1 inhibition produced a modest increase in urinary sodium excretion in male mice of both genotypes but augmented urine flow rate only in male mice. NEU1 blockade strikingly enhanced the natriuretic effect of furosemide and amiloride in male and modestly in mice. Taken together, we conclude that haploinsufficiency disrupts vasopressin-dependent modulation of sodium and water reabsorption by sex-dependently altering ERC-mediated modulation of NKCC2 and ENaC. These findings reveal a novel mechanism by which abnormal ERC activity due to haploinsufficiency potentially contributes to renal dysfunction and hypertension. GRAPHICAL ABSTRACT: AC, adenylyl cyclase; AQP2, aquaporin 2; CD, collecting duct; CNT, connecting tubule; DCT, distal convoluted tubule; EBP, elastin binding protein; , elastin allele; ENaC, epithelial sodium channel; ERC, elastin receptor complex; Gs, stimulatory Gα subunit; NEU1, neuroaminidase1; NKCC2, sodium-potassium-chloride cotransporter; PPCA, protective protein/ cathepsin A; TAL, loop of Henle thick ascending limb; V2R, vasopressin receptor type 2.

View on PubMed →DOI: 10.64898/2026.06.11.731713