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

Previous studies have suggested that aldosterone is potentially involved in the development of motion sickness and that atrial natriuretic peptide (ANP) may inhibit it. Therefore, the present study was conducted to investigate the inhibitory effects of ANP on aldosterone activity in motion sickness and on aldosterone-induced changes in endolymph volume in the inner ear. We found that rotatory stimulation induced an elevation in plasma aldosterone levels, intraperitoneal aldosterone injection caused motion sickness-like responses in both guinea pigs and mice, and ANP inhibited these responses. Moreover, aldosterone injection induced an increase in inner ear endolymph volume in guinea pigs, whereas ANP alleviated this endolymph expansion. In addition, mineralocorticoid receptor (MR) expression was increased in the inner ear tissues after rotatory stimulation and aldosterone injection, and in cultured vestibular epithelial cells after aldosterone treatment, whereas ANP reduced MR expression. In cultured vestibular epithelial cells, ANP reduced the aldosterone-induced nuclear distribution of MR, as well as the expression of ENaC and Na+-K+-ATPase and the membrane distribution of Na+-K+-ATPase. Furthermore, ANP inhibited the aldosterone-induced increase in the intracellular K+ concentration in cells incubated with a simulated endolymph fluid, and the increase in intracellular Na+ concentration in cells incubated with an extracellular solution. In conclusion, the present results suggest that ANP may play an anti-motion sickness role by reducing the plasma aldosterone levels and inhibiting aldosterone-induced endolymph expansion by downregulating downstream target protein expression and activities, thereby altering the resultant ion concentrations in the inner ear epithelial cells.