title: Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene.
abstract: OBJECTIVE
  To evaluate the role of kinins in the hypotensive response to angiotensin converting enzyme inhibition, we compared the blood pressure effects induced by acute or chronic captopril administration in a mouse strain (Bk2r-/-) with disruption of the bradykinin B2 receptor gene and in wild-type controls (J129 Sv mice). A second aim was to determine whether Icatibant, a selective bradykinin B2-receptor antagonist, prevented the blood pressure changes induced by acute captopril administration in Swiss, c57/B16, J129 Sv and Bk2r-/- mice.
  
  
  RESULTS
  Under basal conditions, tail-cuff systolic blood pressure (SBP) and intra-arterial mean blood pressure (MBP) were higher in Bk2r-/- than in J129 Sv (SBP: 132+/-2 versus 113+/-3 mmHg; MBP: 144+/-6 versus 122+/-10 mmHg, P< 0.05 for both comparisons). Acute captopril administration (1 mg/kg body weight, intra-arterially) reduced the MBP of Bk2r-/- and J129 Sv by 36+/-8 and 31+/-7 mmHg, respectively. Swiss and c57/B16 mice showed similar decreases in MBP following captopril. Pretreatment with Icatibant (10 nmol/kg body weight, intra-arterially) did not influence the MBP responses to acute captopril in all the strains. Chronic administration of captopril (approximately 120 mg/kg body weight per day for 2 weeks in drinking water) reduced SBP in either Bk2r-/- or J129 Sv. The magnitude of this response was higher in Bk2r-/- than in J129 Sv (65+/-3 versus 47+/-4 mmHg, respectively, P < 0.01).
  
  
  CONCLUSIONS
  Our results suggest that endogenous kinins do not participate in the hypotensive response to angiotensin converting enzyme inhibition in mice; in Bk2r-/-, the exaggerated blood pressure response to chronic captopril appears to be attributable to interference with unbalanced vasoconstrictor action of the renin-angiotensin system.
authors.affiliation: Institute of Pharmacology, University of Sassari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Emanueli
authors.forename: G R
authors.initials: GR
authors.lastname: Angioni
authors.forename: V
authors.initials: V
authors.lastname: Anania
authors.forename: A
authors.initials: A
authors.lastname: Spissu
authors.forename: P
authors.initials: P
authors.lastname: Madeddu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D017353:Gene Deletion; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C065679:icatibant; D002216:Captopril; D001920:Bradykinin