Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin

• Authors: Jill W. Verlander; Seongun Hong; Vladimir Pech, Emory University; James L Bailey, Emory University; Diana Agazatian, Departments of Medicine; Sharon W. Matthews, Department of Medicine, University of Florida College of Medicine; Thomas M. Coffman, Department of Medicine, Duke University; Thu Le, Department of Medicine, University of Virginia; Tadashi Inagami, Department of Biochemistry, Vanderbilt University; Florence M. Whitehill, Department of Medicine, University of Florida College of Medicine; I. David Weiner, Department of Medicine, University of Florida College of Medicine; Donna B. Farley, Department of Medicine, University of Iowa; Young Hee Kim, Emory University; Susan M Wall, Emory University
• Journal Title: American Journal of Physiology - Renal Physiology
• Volume: Volume 301, Number 6
• Publisher: American Physiological Society | 2011-12, Pages F1314-F1325
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1152/ajprenal.00114.2011
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: angiotensin II type 1 receptor; chloride-bicarbonate exchanger; hypertension; connecting tubule; cortical collecting duct

Abstract

Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl− absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whether angiotensin-induced hypertension is pendrin dependent. While blood pressure was similar in pendrin null and wild-type mice under basal conditions, following 2 wk of angiotensin II administration blood pressure was 31 mmHg lower in pendrin null than in wild-type mice. Thus pendrin null mice have a blunted pressor response to angiotensin II. Further experiments explored the effect of angiotensin on pendrin expression. Angiotensin II administration shifted pendrin label from the subapical space to the apical plasma membrane, independent of aldosterone. To explore the role of the angiotensin receptors in this response, pendrin abundance and subcellular distribution were examined in wild-type, angiotensin type 1a (Agtr1a) and type 2 receptor (Agtr2) null mice given 7 days of a NaCl-restricted diet (< 0.02% NaCl). Some mice received an Agtr1 inhibitor (candesartan) or vehicle. Both Agtr1a gene ablation and Agtr1 inhibitors shifted pendrin label from the apical plasma membrane to the subapical space, independent of the Agtr2 or nitric oxide (NO). However, Agtr1 ablation reduced pendrin protein abundance through the Agtr2 and NO. Thus angiotensin II-induced hypertension is pendrin dependent. Angiotensin II acts through the Agtr1a to shift pendrin from the subapical space to the apical plasma membrane. This Agtr1 action may be blunted by the Agtr2, which acts through NO to reduce pendrin protein abundance.