Enhanced Ca <sup>2+</sup> signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model ( <i>Cacna1h</i> <sup> <i>M1560V/+</i> </sup> )
Eric Seidel, Julia Schewe, Junhui Zhang, Hoang An Dinh, Sofia K. Forslund, Lajos Markó, Nicole Hellmig, Jörg Peters, Dominik N. Müller, Richard P. Lifton, Timothy Nottoli, Gabriel Stölting, Ute I. Scholl
Abstract
Significance Primary aldosteronism (increased production of the adrenal steroid hormone aldosterone) is the most common cause of secondary hypertension. We here generated a mouse model of familial hyperaldosteronism type IV with a heterozygous gain-of-function mutation in a calcium channel gene ( Cacna1h M1560V/+ ). Cacna1h M1560V/+ mice have about twofold elevated aldosterone:renin ratios (a screening parameter for primary aldosteronism) and elevated blood pressure, with an overall mild phenotype. Elevated adrenal aldosterone synthase expression in Cacna1h M1560V/+ mice is associated with increased intracellular calcium concentrations in glomerulosa cells. This model allows for the ex vivo analysis of calcium signaling in aldosterone-producing glomerulosa cells of the adrenal gland. Cacna1h −/− mice have normal aldosterone synthase expression, with implications for the evaluation of CACNA1H as a therapeutic target.