title: Potent antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature.
abstract: BACKGROUND
  Angiotensin type 1 (AT1) receptor-deficient mice (Agtr1-/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intrarenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this renal vascular hypertrophy.
  
  
  METHODS
  Wild-type and Agtr1-/- mice were examined for the developmental regulation pattern of the kinin-kallikrein system and treated with aprotinin (a kallikrein inhibitor), AcLys [D-b Nal7, Ile8] des-Arg9-bradykinin (a bradykinin B1 receptor antagonist), or Hoe-140 (a bradykinin B2 receptor antagonist) from 3 to 14 days of age.
  
  
  RESULTS
  The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1-/- kidneys at 2 and 3 weeks of age. Immunohistochemical staining in Agtr1-/- mice revealed tissue kallikrein staining along the nephron from connecting tubules to cortical collecting tubules in proximity to the hypertrophic vasculature, whereas tissue kallikrein staining was confined to connecting tubules in wild-type mice. Aprotinin and Hoe-140 accelerated the vascular hypertrophy significantly as determined by wall thickness ratio, whereas B1 receptor antagonism had no effect.
  
  
  CONCLUSIONS
  The kinin-kallikrein system in the Agtr1-/- mouse kidney is functionally activated by local suppression of kininase II and extensive redistribution of kallikrein to perivascular areas. This activation, specific to the kidney, serves to dampen a development of the marked vascular hypertrophy. These results demonstrate, to our knowledge for the first time, the antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature in vivo.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2584, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Matsusaka
authors.forename: T E
authors.initials: TE
authors.lastname: Hunley
authors.forename: T
authors.initials: T
authors.lastname: Inagami
authors.forename: A
authors.initials: A
authors.lastname: Fogo
authors.forename: I
authors.initials: I
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001160:Arterioles / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006984:Hypertrophy; D007150:Immunohistochemistry; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology; D007610:Kallikreins / Q000032:analysis / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000235:genetics*; D018002:Receptors, Bradykinin / Q000502:physiology*; D012077:Renal Artery / Q000201:enzymology / Q000473:pathology; D012079:Renal Circulation / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins