AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure.

Gurley SB, Riquier-Brison ADM, Schnermann J, Sparks MA, Allen AM, Haase VH, Snouwaert JN, Le TH, McDonough AA, Koller BH, Coffman TM
Cell Metab. 2011 13 (4): 469-475

PMID: 21459331 · PMCID: PMC3070917 · DOI:10.1016/j.cmet.2011.03.001

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 AT(1) 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.

Copyright © 2011 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Animals Blood Pressure Hypertension Kidney Tubules, Proximal Mice Receptor, Angiotensin, Type 1 Renin-Angiotensin System Signal Transduction Sodium Sodium-Hydrogen Exchanger 3 Sodium-Hydrogen Exchangers Sodium-Potassium-Chloride Symporters Solute Carrier Family 12, Member 1

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