Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene

Paolo Madeddu, Maria Vittoria Varoni, Domenico Palomba, Costanza Emanueli, Maria Piera Demontis, Nicola Glorioso, Paolo Dessì-Fulgheri, Riccardo Sarzani, Vittorio Anania

Research output: Contribution to journalArticlepeer-review

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(-/-)). Methods and 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; P2-receptors by Icatibant (50 nmol/100 g body wt twice a day SC) 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 AT12-receptor antagonist reduced the basal blood pressure of Bk2r(-/-) by 21±3 mm Hg (P1-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.

Original languageEnglish
Pages (from-to)3570-3578
Number of pages9
JournalCirculation
Volume96
Issue number10
Publication statusPublished - Nov 18 1997

Keywords

  • Bradykinin
  • Genes
  • Kinins
  • Receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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