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

Costanza Emanueli, Gabriele Rondoni Angioni, Vittorio Anania, Alessandro Spissu, Paolo Madeddu

Research output: Contribution to journalArticlepeer-review

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. 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.

Original languageEnglish
Pages (from-to)1701-1706
Number of pages6
JournalJournal of Hypertension
Volume15
Issue number12 II
DOIs
Publication statusPublished - Dec 1997

Keywords

  • Angiotensin converting enzyme inhibition
  • B receptors
  • Bradykinin
  • Knock-out mice

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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