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

Abstract

Adenomatous polyposis coli (APC) fosters degradation of β-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.