Regulation of blood pressure by the type 1A angiotensin II receptor gene

Masaki Ito, Michael I. Oliverio, Peter J. Mannon, Christopher F. Best, Nobuyo Maeda, Oliver Smithies, Thomas M. Coffman

Research output: Contribution to journalArticlepeer-review

548 Scopus citations


The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the physiological and genetic functions of the type 1A receptor for angiotensin II, we have disrupted the mouse gene encoding this receptor in embryonic stem cells by gene targeting. Agtr1A(-/-) mice were born in expected numbers, and the histomorphology of their kidneys, heart, and vasculature was normal. AT1 receptor-specific angiotensin II binding was not detected in the kidneys of homozygous Agtr1A(-/-) mutant animals, and Agtr1A(+/-) heterozygotes exhibited a reduction in renal AT1 receptor-specific binding to ≃50% of wild-type [Agtr1A(+/+)] levels. Pressor responses to infused angiotensin II were virtually absent in Agtr1A(-/-) mice and were qualitatively altered in Agtr1A(+/-) heterozygotes. Compared with wild-type controls, systolic blood pressure measured by tail cuff sphygmomanometer was reduced by 12 mmHg (1 mmHg = 133 Pa) in Agtr1A(+/-) mice and by 24 mmHg in Agtr1A(-/-) mice. Similar differences in blood pressure between the groups were seen when intraarterial pressures were measured by carotid cannulation. These studies demonstrate that type 1A angiotensin II receptor function is required for vascular and hemodynamic responses to angiotensin II and that altered expression of the Agtr1A gene has marked effects on blood pressures.

Original languageEnglish (US)
Pages (from-to)3521-3525
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Apr 11 1995
Externally publishedYes


  • G protein-coupled receptor
  • gene targeting
  • hypertension

ASJC Scopus subject areas

  • General


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