Role of Pendrin in the Pathophysiology of Aldosterone-Induced Hypertension.

The recent advances in genetics and molecular biology have resulted in the characterization of key components that critically regulate renal NaCl transport and blood pressure. Pendrin is a Cl-/HCO3- exchanger that is highly expressed in thyroid, inner ear, and kidney. In the kidney, it is selectively present at the apical membrane in non-α intercalated cells of the connecting tubules and cortical collecting duct. Besides its role in acid/base homeostasis, accumulating studies using various genetically modified animals have provided compelling evidence that pendrin regulates extracellular fluid volume and electrolyte balance at the downstream of aldosterone signaling. We have shown that angiotensin II and aldosterone cooperatively control pendrin abundance partly through mammalian target of rapamycin signaling and mineralocorticoid receptor dephosphorylation, which is necessary for the kidney to prevent extracellular fluid loss and electrolyte disturbances under physiologic perturbations. In line with the experimental observations, several clinical data indicated that the impaired pendrin function can cause fluid and electrolyte abnormalities in humans. The purpose of this review is to provide an update on the recent progress regarding the role of pendrin in fluid and electrolyte homeostasis, as well as in the pathophysiology of hypertension associated with mineralocorticoid receptor signaling.