Enhanced Ca²⁺signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model (<i>Cacna1h</i>^{<i>M1560V/+</i>})

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.