AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure

Susan B. Gurley, Anne D.M. Riquier-Brison, Jurgen Schnermann, Matthew A. Sparks, Andrew M. Allen, Volker H. Haase, John N. Snouwaert, Thu H. Le, Alicia A. McDonough, Beverley H. Koller, Thomas M. Coffman

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Hypertension affects more than 1.5 billion people worldwide but the precise cause of elevated blood pressure (BP) cannot be determined in most affected individuals. Nonetheless, blockade of the renin-angiotensin system (RAS) lowers BP in the majority of patients with hypertension. Despite its apparent role in hypertension pathogenesis, the key cellular targets of the RAS that control BP have not been clearly identified. Here we demonstrate that RAS actions in the epithelium of the proximal tubule have a critical and nonredundant role in determining the level of BP. Abrogation of AT1 angiotensin receptor signaling in the proximal tubule alone is sufficient to lower BP, despite intact vascular responses. Elimination of this pathway reduces proximal fluid reabsorption and alters expression of key sodium transporters, modifying pressure-natriuresis and providing substantial protection against hypertension. Thus, effectively targeting epithelial functions of the proximal tubule of the kidney should be a useful therapeutic strategy in hypertension.

Original languageEnglish (US)
Pages (from-to)469-475
Number of pages7
JournalCell Metabolism
Volume13
Issue number4
DOIs
StatePublished - Apr 6 2011

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Gurley, S. B., Riquier-Brison, A. D. M., Schnermann, J., Sparks, M. A., Allen, A. M., Haase, V. H., Snouwaert, J. N., Le, T. H., McDonough, A. A., Koller, B. H., & Coffman, T. M. (2011). AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metabolism, 13(4), 469-475. https://doi.org/10.1016/j.cmet.2011.03.001