Atrial natriuretic peptide may inhibit motion sickness through reducing aldosterone-induced increase in endolymph volume of the inner ear

Rotatory stimulation and the administration of aldosterone trigger physiological changes in the inner ear that correlate with motion sickness-like responses, specifically increased endolymph volume and altered vestibular function. This process appears to be mediated by the upregulation of mineralocorticoid receptors (MR) and downstream target proteins, including the epithelial sodium channel (ENaC) and Na+-K+-ATPase (NKA), which disrupt ionic homeostasis in vestibular epithelial cells.
Atrial natriuretic peptide (ANP) acts as an inhibitor in this pathway. ANP reduces plasma aldosterone levels and suppresses the expression and nuclear translocation of MR, thereby preventing the expansion of endolymph volume and attenuating behavioral signs of motion sickness. While these results suggest a potential therapeutic target for anti-motion sickness agents that avoid central nervous system side effects, the causal link between endolymph expansion and motion sickness remains indirect. Further research is required to determine if inhibiting endolymph volume directly suppresses motion sickness in larger animal models and humans.

* Lu Q-C, Ji W, Li X, Ge J-G, Xu L-H, and Jiang Z-L published research in PLoS One on September 25, 2026.
* The study involved guinea pigs, ICR mice, and P8 mouse pups.
* Rotatory stimulation increased plasma aldosterone levels in guinea pigs.
* Intraperitoneal aldosterone injections induced conditioned taste aversion (CTA) in guinea pigs and mice.
* Aldosterone injections increased the curvature of swim trajectories in guinea pigs.
* Aldosterone injections increased endolymph volume in the cochlea of guinea pigs.
* Atrial natriuretic peptide (ANP) administration inhibited the elevation of plasma aldosterone and the subsequent behavioral and physiological responses.
* Aldosterone treatment increased mineralocorticoid receptor (MR) expression and nuclear translocation in vestibular epithelial cells.
* Aldosterone upregulated ENaC and Na+-K+-ATPase (NKA) expression.
* ANP reduced MR, ENaC, and NKA expression and inhibited aldosterone-induced intracellular K+ and Na+ increases.
* The research was funded by the National Natural Science Foundation of China.

This study utilizes a rigorous academic framework to propose a peripheral mechanism for motion sickness, moving the focus away from the central nervous system toward the ionic balance of the inner ear. The methodology is comprehensive, employing a combination of in vivo behavioral tests (CTA, swim trajectory), advanced imaging (MRI), and in vitro cellular analysis. However, a peer reviewer would note the reliance on surrogate markers; conditioned taste aversion and swim curvature are proxies for the complex human experience of motion sickness. Additionally, the sample sizes for MRI quantification (n=3-4) are small, increasing the risk of variance.
The authors are cautious, explicitly acknowledging that they measured cochlear endolymph rather than vestibular endolymph and that the causal chain—from aldosterone to endolymph expansion to behavioral sickness—is currently an inference based on correlation. The claim that ANP inhibits motion sickness is proportionate to the data, provided one accepts the animal models as valid surrogates.
The real-world implication is the potential for "peripheral-only" drugs. If MR antagonists or NPR-A agonists can be engineered to act solely within the inner ear without crossing the blood-brain barrier, the debilitating CNS side effects of current antihistamines (sedation, blurred vision) could be eliminated.
To strengthen these findings, a follow-up study should employ a direct MR antagonist in the inner ear to see if it mimics the effect of ANP without affecting systemic aldosterone levels. This would isolate the receptor's role from the hormone's systemic effects.
Bridge Questions:
1. If endolymph expansion is the primary driver, why do some individuals with similar vestibular profiles not experience motion sickness?
2. Could systemic administration of ANP or MR antagonists trigger adverse cardiovascular or renal effects that outweigh the benefits of treating motion sickness?