Details

Autor(en) / Beteiligte

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

Titel

AT1A Angiotensin Receptors in the Renal Proximal Tubule Regulate Blood Pressure

Ist Teil von

• Cell metabolism, 2011-04, Vol.13 (4), p.469-475

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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. ▴ AT1A angiotensin receptors in kidney proximal tubule regulate blood pressure ▴ AT1A receptors provide tonic control of fluid reabsorption by the proximal tubule ▴ Elimination of AT1A receptors from proximal tubule attenuates hypertension ▴ Reduced expression of key sodium transporters explains improved hypertension