title: Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor.
abstract: BACKGROUND
  The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats.
  
  
  METHODS
  In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319.
  
  
  RESULTS
  The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only.
  
  
  CONCLUSIONS
  In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin-angiotensin system for the improvement of renal function in term and, in particular, preterm infants.
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Russell D
authors.initials: RD
authors.lastname: Brown
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Lucinda M
authors.initials: LM
authors.lastname: Hilliard
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Mirabito
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Wirth
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Firth
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Australia.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans
authors.affiliation: Department of Physiology, Monash University, Melbourne, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319