Primary aldosteronism (PA) is the major cause of secondary hypertension and represents approximately 10% of all hypertensive subjects. PA patient hypertension results from inappropriate activation of kidney mineralocorticoid receptors (MR). MR activation can occur due to aldosterone, other MR ligands, or as a result of antagonists of the enzyme that protects MR from over-activation [11β-hydroxysteroid dehydrogenase (HSD11B2)]. Defining disease-related MR agonists or HSD11B2 antagonist has been limited by the lack of appropriate in vitro models. We will develop a “dual” high throughput cell-based model to define novel MR / HSD11B2 agonists and antagonists. Discovery of disease-related agonists/antagonists will lead to NIH grant proposals that focus on the role of these compounds in human disease. Goals: a) Develop a dual high-throughput model for MR agonist and HSD11B2 antagonists. b) Screen serum samples for MR agonists or HSD11B2 antagonists.