Ayuzawa N, Nishimoto M, Ueda K, et al. - Given the importance of sodium chloride transport regulation in the aldosterone-sensitive distal nephron for fluid homeostasis and BP control, and regulation of sodium chloride handling (which is controlled by the renin-angiotensin-aldosterone system) complementarily by pendrin (chloride-bicarbonate exchanger in β-intercalated cells) along with NCC (sodium chloride cotransporter in distal convoluted tubules), researchers assessed the mechanism as well as the roles of pendrin upregulation through mineralocorticoid receptor in two distinct models of renin-angiotensin-aldosterone system activation in this study utilizing mice with mineralocorticoid receptor deletion in intercalated cells. To determine the role of pendrin regulation in salt-sensitive hypertension, they employed aldosterone-treated NCC knockout mice. Findings revealed that two pathways of pendrin upregulation, provoked by angiotensin II via mineralocorticoid receptor activation in intercalated cells and by alkalosis via mineralocorticoid receptor activation in principal cells, together with NCC, have crucial roles in fluid homeostasis during salt depletion as well as salt-sensitive hypertension mediated by aldosterone excess.