title: Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated.
abstract: OBJECTIVE
  Angiotensin (Ang) IV was reported to induce renal vasoconstriction or vasodilation in rats via AT1 or AT4 receptors, respectively, whereby the latter one has been identified to be the insulin-regulated aminopeptidase (IRAP). We investigated the effects of Ang IV on mean arterial pressure (MAP) and renal cortical blood flow (CBF) in AT1a, AT1b, AT2 receptor and IRAP knockout (-/-) mice and their corresponding wild-type littermates. Ang II, known as a renal vasoconstrictor in mice, was used as a reference.
  
  
  METHODS
  MAP was recorded via a femoral catheter and CBF was measured using a light amplification by stimulated emission of radiation (LASER) Doppler probe; cortical vascular resistance (CVR) was calculated as MAP divided by CBF.
  
  
  RESULTS
  Baseline MAP, CBF and CVR in AT1a (-/-) mice were significantly lower than wild-type mice. AT2 (-/-) mice had a significantly higher baseline MAP, but similar CBF. In wild-type mice, Ang IV and Ang II induced dose-dependent pressor and renal vasoconstrictor responses, which were antagonized by the AT1 receptor blocker candesartan. These responses were almost completely absent in AT1a (-/-) mice, but were enhanced in AT2 (-/-) mice; responses in AT1b (-/-) and IRAP (-/-) mice were comparable to those in corresponding wild-type mice.
  
  
  CONCLUSIONS
  Ang IV mediates pressure and renal vasoconstrictor effects in mice via AT1a receptors, whereas IRAP/AT4 is not involved.
authors.affiliation: Department of Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090-Brussels, Belgium.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Florian
authors.initials: F
authors.lastname: Gembardt
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanderheyden
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Albiston
authors.forename: Siew Yeen
authors.initials: SY
authors.lastname: Chai
authors.forename: Alain G
authors.initials: AG
authors.lastname: Dupont
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001835:Body Weight; D017931:DNA Primers; D019332:Endothelin-1 / Q000494:pharmacology; D006439:Hemodynamics; D007668:Kidney / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017931:DNA Primers; D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C081643:candesartan