Dietary K+ supplementation restores normal aldosterone level in Na+-deprived renal tubule-specific CAP1/Prss8-deficient mice.

We previously reported that Na+-deprived mice lacking CAP1/Prss8 in kidney tubules maintained epithelial sodium channel-mediated sodium balance albeit persistent hypoaldosteronism, hence indicating an uncoupling from aldosterone production. This further suggested an implication of the serine protease CAP1/Prss8 (prostasin) in the cross talk of the kidney with the adrenal gland that does not express prostasin. When these knockout (Ko) mice were additionally exposed to a high K+ diet, plasma K+ levels and plasma aldosterone concentrations were normalized and no longer different from those of the control mice. The mRNA transcript expression of the adrenal aldosterone synthase Cyp11b2, which was lower in Na+-deprived CAP1/Prss8 Ko animals, was in the normal range. Plasma aldosterone levels were similar to control animals, indicating that K+ rescued the hypoaldosteronism in Na+-deprived CAP1/Prss8 Ko animals. These data suggest that CAP1/Prss8 (prostasin) is implicated in the regulation of aldosterone synthesis or production and that the consequences of CAP1/Prss8 deficiency can be compensated by high dietary K+ supplementation. Prostasin may therefore present a promising regulator of aldosterone production by affecting the adrenal steroidogenic pathway.NEW & NOTEWORTHY We explore the role of the serine protease CAP1/Prss8 in aldosterone synthesis. Described previously as a candidate gene for hypertension, the mechanism by which renal serine protease deficiency is implicated in aldosterone production is still largely unknown. Our findings underscore a role of prostasin in the regulation of aldosterone synthesis. In kidney-specific CAP1/Prss8 knockout mice, K+ supplementation is predominant over Na+ and restores normal aldosterone production proposing new pathways to treat hypo- or hypertension.