Hyperaldosteronism, hypervolemia, and increased blood pressure in mice expressing defective APC.

Adenomatous polyposis coli (APC) fosters degradation of beta-catenin, a multifunctional protein upregulating the serum- and glucocorticoid-inducible kinase (SGK1). SGK1 regulates a wide variety of renal transport processes. The present study explored the possibility that APC influences renal function. To this end, metabolic cage experiments were performed in mice carrying a loss-of-function mutation in the APC gene (apc(Min/+)), their wild-type littermates (apc(+/+)), and apc(Min/+) mice lacking functional SGK1 (apc(Min/+)/sgk1(-/-)). As a result, mean body weight, food intake, fluid intake, salt appetite, urinary flow, as well as plasma Na(+) and K(+) concentrations were similar in apc(Min/+) mice, apc(+/+) mice, and apc(Min/+)/sgk1(-/-) mice. Glomerular filtration rate and absolute renal Na(+) excretion were decreased, and fractional urinary K(+) excretion was enhanced in apc(Min/+) mice. The antinatriuresis, but not the hypofiltration and kaliuresis was partially reversed by additional lack of SGK1. Plasma corticosterone and aldosterone concentrations were significantly enhanced in apc(Min/+) mice. While the plasma corticosterone concentration was similar in apc(+/+) mice and apc(Min/+)/sgk1(-/-) mice, plasma aldosterone was even higher in apc(Min/+)/sgk1(-/-) mice than in apc(Min/+) mice. The hyperaldosteronism of apc(Min/+) mice was paralleled by significantly elevated plasma volume and blood pressure. The experiments reveal an influence of defective APC on adrenal hormone release and renal function, effects partially but not completely explained by APC dependence of SGK1 expression.