Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene

J Hypertens. 1997 Dec;15(12 Pt 2):1701-6. doi: 10.1097/00004872-199715120-00075.


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.

Methods and 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Bradykinin / administration & dosage
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists
  • Captopril / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Gene Deletion*
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Mice
  • Mice, Knockout / genetics
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / genetics
  • Receptors, Bradykinin / physiology*
  • Vasoconstriction / drug effects


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Bradykinin Receptor Antagonists
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • icatibant
  • Captopril
  • Bradykinin