title: Proximal tubule angiotensinogen modulation of arterial pressure.
abstract: OBJECTIVE
  Although the existence of a complete intrarenal renin-angiotensin system is now well established, its role in modulating tubule sodium transport and blood pressure is incompletely understood. Several recent studies have shed light on one component of the system, proximal tubule-derived angiotensinogen (AGT). This review discusses the synthesis, regulation and function of AGT in the proximal tubule.
  
  
  RESULTS
  Under normal sodium intake, AGT within the S1 and S2 segments of the proximal tubule may derive from the systemic circulation, whereas the S3 segment synthesizes AGT. Urinary AGT likely primarily reflects proximal tubule-derived AGT. Proximal tubule AGT synthesis is regulated by high Na intake, angiotensin-II and inflammatory cytokines. Transgenic expression of mouse AGT in the proximal tubule causes hypertension. Overexpression of rat AGT in the proximal tubule leads to hypertension, enhanced reactive oxygen species generation via NADPH oxidase, tubular apoptosis and tubulointerstitial fibrosis; these effects can be mitigated by catalase overexpression.
  
  
  CONCLUSIONS
  Proximal tubule-derived AGT has the potential to modulate blood pressure and sodium balance, and promote renal injury. Interactions with the systemic renin-angiotensin system may influence the role of proximal tubule-derived AGT in the kidney.
authors.affiliation: Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Ramkumar
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000808:Angiotensinogen / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D000808:Angiotensinogen; D012964:Sodium