Overexpression of mouse angiotensinogen in renal proximal tubule causes salt-sensitive hypertension in mice

Am J Hypertens. 2012 Jun;25(6):684-9. doi: 10.1038/ajh.2012.16. Epub 2012 Mar 1.


Background: The role of proximal tubule (PT) angiotensinogen (AGT) in modulating blood pressure has previously been examined using mice expressing PT human AGT and human renin, or rat AGT. These animals are hypertensive; however, the question remains whether alterations in mouse PT AGT alone affects arterial pressure.

Methods: Mouse AGT cDNA was knocked-in to the endogenous kidney androgen protein (KAP) gene using an internal ribosomal entry site (IRES)-based strategy.

Results: The KAP-mAGT animals showed kidney-specific KAP-AGT mRNA expression; renal in situ hybridization detected KAP-AGT mRNA only in PT. Urinary AGT was markedly increased in KAP-mAGT mice. On a high Na diet, radiotelemetric arterial pressure showed a systolic pressure elevation; no significant difference in arterial pressure was observed on a normal diet. Plasma renin concentration (PRC) was reduced in KAP-mAGT animals given a high Na diet, but was not different between mouse lines during normal Na intake. Plasma AGT concentration was not altered by overexpression of PT mouse AGT.

Conclusions: In summary, PT overexpression of mouse AGT leads to salt-sensitive hypertension without recruitment of the systemic renin-angiotensin system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism*
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Chimera / genetics
  • Disease Models, Animal
  • Female
  • Gene Knock-In Techniques
  • Hypertension / chemically induced*
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Kidney Tubules, Proximal / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Renin / blood
  • Renin-Angiotensin System / physiology
  • Sodium Chloride, Dietary / adverse effects*
  • Sodium Chloride, Dietary / pharmacology


  • RNA, Messenger
  • Sodium Chloride, Dietary
  • Angiotensinogen
  • Renin