Mitochondrial function in aldosterone-dependent human hypertension

This study presents a user-friendly, custom-made pipeline to detect and quantify intracellular calcium [Ca²⁺]i oscillations, validated in human aldosterone-producing adrenocortical cells. It enabled the first characterization of [Ca²⁺]i dynamics in primary human cells, showing that aldosterone-producing adenoma (APA) cells have lower basal calcium due to increased organelle sequestration, but exhibit heightened oscillations upon Ang II stimulation, promoting aldosterone overproduction. Ang II acts via the AT1 receptor, confirmed through irbesartan inhibition, and [Ca²⁺]i oscillations are regulated by Task 2 potassium channels and others. The study highlights that multicellular rosette organization supports synchronized calcium signaling, suggesting tissue-level coordination. APA cells also show reduced mitochondrial reactive oxygen species, indicating protective adaptations. Additionally, APA patient serum induced vascular smooth muscle calcification in vitro, linking findings to cardiovascular risk in primary aldosteronism (PA). This research offers novel insights into adrenal calcium signaling and potential therapeutic targets for aldosterone-driven cardiovascular disease.