Depolarisation of adrenal zona glomerulosa cells is a pivotal event for the secretion of aldosterone. Potassium channels like TASK1 and TASK3 are highly expressed in the adrenal cortex and determine the membrane voltage. TASK3^-/- mice showed a severe age-dependent hyperaldosteronism. Therefore, the aim of this study was to identify the mechanisms underlying this age-dependent hyperaldosteronism.

Neonatal TASK3^-/- mice (ko) showed higher plasma aldosterone levels compared to wildtype (wt) animals correlating with an increased adrenal mRNA expression level of the aldosterone-synthase. These high aldosterone levels decreased within the first two weeks of life. Plasma concentrations of progesterone and corticosterone showed the same age-dependent dysregulation. These results pointed to a broader adrenal dysfunction in newborn ko mice. A chip-based analysis was performed to measure differential gene expression in adrenals of 1 and 12 day old mice. Interestingly, adrenal renin mRNA was strongly upregulated in newborn ko mice, but decreased to normal wt levels in 12 day old mice. The high renin gene expression was confirmed by realtime PCR and by renin-specific immunofluorescence.

These data suggest that transient activation of the local adrenal renin-angiotensin-system contributes to the hyperaldosteronism of neonatal TASK3^-/- mice. Future studies are needed to investigate the signal pathways resulting in increased adrenal renin production and to identify the compensation mechanisms present in adult mice.