Severe Hyperaldosteronism in Neonatal Task3 Potassium Channel Knockout Mice Is Associated With Activation of the Intraadrenal Renin-Angiotensin System

Abstract

Abstract Task3 K+ channels are highly expressed in the adrenal cortex and contribute to the angiotensin II and K+ sensitivity of aldosterone-producing glomerulosa cells. Adult Task3−/− mice display a partially autonomous aldosterone secretion, subclinical hyperaldosteronism, and salt-sensitive hypertension. Here, we investigated the age dependence of the adrenal phenotype of Task3−/− mice. Compared with adults, newborn Task3−/− mice displayed a severe adrenal phenotype with strongly increased plasma levels of aldosterone, corticosterone, and progesterone. This adrenocortical dysfunction was accompanied by a modified gene expression profile. The most strongly up-regulated gene was the protease renin. Real-time PCR corroborated the strong increase in adrenal renin expression, and immunofluorescence revealed renin-expressing cells in the zona fasciculata. Together with additional factors, activation of the local adrenal renin system is probably causative for the severely disturbed steroid hormone secretion of neonatal Task3−/− mice. The changes in gene expression patterns of neonatal Task3−/− mice could also be relevant for other forms of hyperaldosteronism.