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 language | English |
|---|---|
| Pages (from-to) | 391-396 |
| Number of pages | 6 |
| Journal | Hypertension |
| Volume | 35 |
| Issue number | 1 II |
| Publication status | Published - Jan 2000 |
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Keywords
- Angiotensin
- Blood pressure
- Bradykinin
- Genes
- Heart failure
- Myocardium hypertrophy
ASJC Scopus subject areas
- Internal Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Angiotensin II type I receptor blockade prevents cardiac remodeling in bradykinin B2 receptor knockout mice
AU - Madeddu, Paolo
AU - Emanueli, Costanza
AU - Maestri, Roberta
AU - Salis, Maria Bonaria
AU - Minasi, Alessandra
AU - Capogrossi, Maurizio C.
AU - Olivetti, Giorgio
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
KW - Angiotensin
KW - Blood pressure
KW - Bradykinin
KW - Genes
KW - Heart failure
KW - Myocardium hypertrophy
UR - http://www.scopus.com/inward/record.url?scp=0033966333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033966333&partnerID=8YFLogxK
M3 - Article
C2 - 10642330
AN - SCOPUS:0033966333
VL - 35
SP - 391
EP - 396
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 1 II
ER -