title: Overexpression of mouse angiotensinogen in renal proximal tubule causes salt-sensitive hypertension in mice.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Ying
authors.forename: Deborah
authors.initials: D
authors.lastname: Stuart
authors.forename: Elaine
authors.initials: E
authors.lastname: Hillas
authors.forename: Barbu R
authors.initials: BR
authors.lastname: Gociman
authors.forename: Nirupama
authors.initials: N
authors.lastname: Ramkumar
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lalouel
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002678:Chimera / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen; D012083:Renin