• Media type: E-Article
  • Title: Severe Hyperaldosteronism in Neonatal Task3 Potassium Channel Knockout Mice Is Associated With Activation of the Intraadrenal Renin-Angiotensin System
  • Contributor: Bandulik, Sascha; Tauber, Philipp; Penton, David; Schweda, Frank; Tegtmeier, Ines; Sterner, Christina; Lalli, Enzo; Lesage, Florian; Hartmann, Michaela; Barhanin, Jacques; Warth, Richard
  • Source: Endocrinology ; 154 ( 2013 ) S. 2712-2722
  • Published: The Endocrine Society, 2013
  • Language: English
  • DOI: 10.1210/en.2013-1101
  • ISSN: 0013-7227; 1945-7170
  • Keywords: Endocrinology
  • Abstract: <jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
  • Description: <jats:title>Abstract</jats:title>
    <jats:p>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.</jats:p>