Enhanced Ca2+signaling, mild primary aldosteronism, and hypertension in a familial hyperaldosteronism mouse model (Cacna1hM1560V/+)

• DOI: 10.1073/pnas.2014876118
• Publication Date: 2021-04-20T21:25:43Z
• Authors: Eric Seidel; Julia Schewe; Junhui Zhang; Hoang An Dinh; Sofia K. Forslund; Lajos Markó; Nicole Hellmig; Jörg Peters; Dominik N. Muller; Richard P. Lifton; Timothy Nottoli; Gabriel Stölting; Ute I. Scholl
• Keywords: Hyperaldosteronism; Aldosterone synthase; Primary Aldosteronism; Steroid 11-beta-hydroxylase; Steroid hormone

Significance Primary aldosteronism (increased production of the adrenal steroid hormone aldosterone) is most common cause secondary hypertension. We here generated a mouse model familial hyperaldosteronism type IV with heterozygous gain-of-function mutation in calcium channel gene ( Cacna1h M1560V/+ ). mice have about twofold elevated aldosterone:renin ratios (a screening parameter for primary aldosteronism) and blood pressure, an overall mild phenotype. Elevated aldosterone synthase expression associated increased intracellular concentrations glomerulosa cells. This allows ex vivo analysis signaling aldosterone-producing cells gland. −/− normal expression, implications evaluation CACNA1H as therapeutic target.