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 journalArticle

Abstract

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
JournalHypertension
Volume35
Issue number1 II
Publication statusPublished - Jan 2000

Fingerprint

Bradykinin B2 Receptors
Angiotensin I
Angiotensin Receptors
Knockout Mice
Angiotensin II
Bradykinin
A 81988
Blood Pressure
Fibrosis
Heart Rate
Angiotensin II Type 1 Receptor Blockers
Weights and Measures
Ventricular Remodeling
Plethysmography
Cardiomegaly
Tail
Hypertension
Genes

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Madeddu, P., Emanueli, C., Maestri, R., Salis, M. B., Minasi, A., Capogrossi, M. C., & Olivetti, G. (2000). Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice. Hypertension, 35(1 II), 391-396.

Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice. / Madeddu, Paolo; Emanueli, Costanza; Maestri, Roberta; Salis, Maria Bonaria; Minasi, Alessandra; Capogrossi, Maurizio C.; Olivetti, Giorgio.

In: Hypertension, Vol. 35, No. 1 II, 01.2000, p. 391-396.

Research output: Contribution to journalArticle

Madeddu, P, Emanueli, C, Maestri, R, Salis, MB, Minasi, A, Capogrossi, MC & Olivetti, G 2000, 'Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice', Hypertension, vol. 35, no. 1 II, pp. 391-396.
Madeddu P, Emanueli C, Maestri R, Salis MB, Minasi A, Capogrossi MC et al. Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice. Hypertension. 2000 Jan;35(1 II):391-396.
Madeddu, Paolo ; Emanueli, Costanza ; Maestri, Roberta ; Salis, Maria Bonaria ; Minasi, Alessandra ; Capogrossi, Maurizio C. ; Olivetti, Giorgio. / Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice. In: Hypertension. 2000 ; Vol. 35, No. 1 II. pp. 391-396.
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