title: Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene.
abstract: BACKGROUND
  To evaluate the role of kinins in the regulation of cardiovascular function, we studied the phenotype of a mouse strain with disruption of the bradykinin B2-receptor gene (Bk 2r-/-).
  
  
  RESULTS
  Under basal conditions, tail-cuff blood pressure was higher in Bk2r-/- than in wild-type Bk2r+/+ and heterozygous Bk2r+/- mice (124+/-1 versus 109+/-1 and 111+/-2 mm Hg, respectively; P<.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r-/- than in Bk2r+/+ and Bk2r+/- mice (505+/-10 versus 449+/-12 and 477+/-10 mg/100 g body wt, P<.05). Chronic blockade of B2-receptors by Icatibant (50 nmol/100 g body wt twice a day S.C.) or inhibition of nitric oxide synthase by nitro-L-arginine-methyl ester (0.14 mmol/100 g body wt orally) increased the blood pressure of Bk2r+/+ to the levels of Bk2r-/- mice. Compared with the wild-type strain, both Bk2r-/- and Bk2r+/- mice showed exaggerated vasopressor responses to angiotensin II. In addition, chronic administration of an angiotensin AT1-receptor antagonist reduced the basal blood pressure of Bk2r-/- by 21+/-3 mmHg (P<.05) to the levels of Bk2r+/+. No difference was detected between strains as far as plasma renin activity and the expression of renin and AT1-receptor genes are concerned. Chronic salt loading (0.84 mmol/g chow for 15 days) increased the blood pressure of Bk2r-/- and Bk2r+/- by 34+/-3 and 14+/-6 mm Hg, respectively, whereas it was ineffective in Bk2r+/+.
  
  
  CONCLUSIONS
  Our results suggest that a normally functioning B2-receptor is essential for the maintenance of cardiovascular homeostasis in mice. Dysfunction of the kallikrein-kinin system could contribute to increase blood pressure levels by leaving the activity of vasoconstrictor agents unbalanced.
authors.affiliation: Clinica Medica, University of Sassari, Italy. madeddu@ssmain.uniss.it
authors.forename: P
authors.initials: P
authors.lastname: Madeddu
authors.forename: M V
authors.initials: MV
authors.lastname: Varoni
authors.forename: D
authors.initials: D
authors.lastname: Palomba
authors.forename: C
authors.initials: C
authors.lastname: Emanueli
authors.forename: M P
authors.initials: MP
authors.lastname: Demontis
authors.forename: N
authors.initials: N
authors.lastname: Glorioso
authors.forename: P
authors.initials: P
authors.lastname: Dessì-Fulgheri
authors.forename: R
authors.initials: R
authors.lastname: Sarzani
authors.forename: V
authors.initials: V
authors.lastname: Anania
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D065168:Bradykinin Receptor Antagonists; D002320:Cardiovascular Physiological Phenomena; D004039:Diet, Sodium-Restricted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009539:Nicotinic Acids / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics; D018002:Receptors, Bradykinin / Q000819:agonists / Q000235:genetics*; D012083:Renin / Q000235:genetics; D013045:Species Specificity; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D009539:Nicotinic Acids; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D013777:Tetrazoles; D000804:Angiotensin II; C081174:A 81988; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester