Reduced hypertension-induced end-organ damage in mice lacking cardiac and renal angiotensinogen synthesis

Ningling Kang, Thomas Walther, Xiao Li Tian, Jürgen Bohlender, Akiyoshi Fukamizu, Detlev Ganten, Michael Bader

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Hypertension-induced damage of kidney and heart is of major clinical relevance, but its pathophysiology is only partially understood. As there is considerable evidence for involvement of angiotensin II, we generated a new mouse model by breeding angiotensinogen (AOGEN) deficient mice with transgenic animals expressing the rat AOGEN gene only in brain and liver. This genetic manipulation overcame the hypotension of AOGEN-deficient mice and even caused hypertension indistinguishable in its extent from the parent transgenic mice with an intact endogenous AOGEN gene. In contrast to normal mice, however, crossbred animals lacked detectable expression of AOGEN in kidney and heart. As a consequence they showed markedly reduced cardiac hypertrophy and fibrosis. Furthermore, hypertension-induced alterations in kidney histology and function were less pronounced in crossbred mice than in equally hypertensive animals expressing AOGEN locally. The dysmorphogenesis observed in kidneys from AOGEN-deficient mice was absent in mice expressing this gene only in liver and brain. Our results support an important role of local AOGEN expression in hypertension-induced end-organ damage but not in the development of the kidney.

Original languageEnglish (US)
Pages (from-to)359-366
Number of pages8
JournalJournal of Molecular Medicine
Volume80
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Blood pressure regulation
  • Damage to kidney and heart
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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    Kang, N., Walther, T., Tian, X. L., Bohlender, J., Fukamizu, A., Ganten, D., & Bader, M. (2002). Reduced hypertension-induced end-organ damage in mice lacking cardiac and renal angiotensinogen synthesis. Journal of Molecular Medicine, 80(6), 359-366. https://doi.org/10.1007/s00109-002-0326-6