Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney

Steven D. Crowley, Susan B. Gurley, Maria J. Herrera, Phillip Ruiz, Robert Griffiths, Anil P. Kumar, Hyung Suk Kim, Oliver Smithies, Thu H. Le, Thomas M. Coffman

Research output: Contribution to journalArticle

429 Scopus citations

Abstract

Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.

Original languageEnglish (US)
Pages (from-to)17985-17990
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number47
DOIs
StatePublished - Nov 21 2006

Keywords

  • Blood pressure
  • Kidney transplantation
  • Transgenic mice

ASJC Scopus subject areas

  • General

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    Crowley, S. D., Gurley, S. B., Herrera, M. J., Ruiz, P., Griffiths, R., Kumar, A. P., Kim, H. S., Smithies, O., Le, T. H., & Coffman, T. M. (2006). Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proceedings of the National Academy of Sciences of the United States of America, 103(47), 17985-17990. https://doi.org/10.1073/pnas.0605545103