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Cell Metab. 2011 Apr 6;13(4):469-475. doi: 10.1016/j.cmet.2011.03.001.

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

Author information

1
Division of Nephrology, Department of Medicine, Duke University and Durham, VA Medical Centers, Durham, NC 27710, USA.
2
Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
3
National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
4
Department of Physiology, University of Melbourne, Melbourne, Victoria 3010, Australia.
5
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
6
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
7
Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
8
Division of Nephrology, Department of Medicine, Duke University and Durham, VA Medical Centers, Durham, NC 27710, USA; Cardiovascular and Metabolic Disorders Research Program, Duke-NUS Graduate Medical School, Singapore 169857. Electronic address: tcoffman@duke.edu.

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 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.

PMID:
21459331
PMCID:
PMC3070917
DOI:
10.1016/j.cmet.2011.03.001
[Indexed for MEDLINE]
Free PMC Article

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