Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice

Paolo Madeddu, Costanza Emanueli, Roberta Maestri, Maria Bonaria Salis, Alessandra Minasi, Maurizio C. Capogrossi, Giorgio Olivetti

Research output: Contribution to journalArticlepeer-review


Knockout mice (B2(-/-) lacking the bradykinin (BK) B2 receptor gene develop mild hypertension, cardiac hypertrophy, and myocardial damage. We hypothesized that these effects are due to the hypertrophying and damaging actions of angiotensin II (Ang II) in the absence of the balancing protection of BK. To verify this hypothesis, B2(-/-) or wild-type mice (B2(+/+) were administered a nonpeptide antagonist of Ang II type 1 (AT1) receptors (A81988) from conception through 180 days of age. Untreated B2(+/+) and B2(- /-) served as controls. Blood pressure (BP) and heart rate were monitored with the use of tail-cuff plethysmography at regular intervals. Ventricular weights, diameters, wall thickness, chamber volume, and myocardial fibrosis were measured at 40 and 180 days. No differences were observed in BP, heart rate, and cardiac weight and dimensions between treated and untreated B2(+/+). The BP of AT1 antagonist-treated B2(-/-) was reduced until 70 days; then, it increased to the levels found in untreated B2(-/-). AT1 receptor blockade resulted in a reduction in left ventricular mass, chamber volume, and wall thickness and abrogated myocardial fibrosis in B2(-/-). These results indicate that Ang II is the major factor responsible for ventricular remodeling and myocardial damage in mice with disruption of BK B2 receptor signaling. The interaction of Ang II and BK appears to be essential for the development of a normal heart.

Original languageEnglish
Pages (from-to)391-396
Number of pages6
Issue number1 II
Publication statusPublished - Jan 2000


  • Angiotensin
  • Blood pressure
  • Bradykinin
  • Genes
  • Heart failure
  • Myocardium hypertrophy

ASJC Scopus subject areas

  • Internal Medicine


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