Acute genetic ablation of pendrin lowers blood pressure in mice

Abstract

Background. Pendrin, the chloride/bicarbonate exchanger of b-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure. Methods. Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued. Therefore, our genetic strategy allows us to test selectively the acute effects of loss of pendrin function. Results. We show that acute loss of pendrin leads to a significant decrease of blood pressure. In addition, acute ablation of pendrin did not alter significantly the acid-base status or blood K+concentration. Conclusion. By using a transgenic mouse model, avoiding offtarget effects related to pharmacological compounds, this study suggests that pendrin could be a novel target to treat hypertension.