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 journalArticle

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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

Fingerprint

Bradykinin B2 Receptors
Phenotype
Blood Pressure
Genes
Kallikrein-Kinin System
Kinins
Angiotensin Receptor Antagonists
Vasoconstrictor Agents
Nitric Oxide Synthase
Angiotensin II
Tail
Homeostasis
Salts
Maintenance
Hypertension

Keywords

  • Bradykinin
  • Genes
  • Kinins
  • Receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Madeddu, P., Varoni, M. V., Palomba, D., Emanueli, C., Demontis, M. P., Glorioso, N., ... Anania, V. (1997). Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. Circulation, 96(10), 3570-3578.

Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. / Madeddu, Paolo; Varoni, Maria Vittoria; Palomba, Domenico; Emanueli, Costanza; Demontis, Maria Piera; Glorioso, Nicola; Dessì-Fulgheri, Paolo; Sarzani, Riccardo; Anania, Vittorio.

In: Circulation, Vol. 96, No. 10, 18.11.1997, p. 3570-3578.

Research output: Contribution to journalArticle

Madeddu, P, Varoni, MV, Palomba, D, Emanueli, C, Demontis, MP, Glorioso, N, Dessì-Fulgheri, P, Sarzani, R & Anania, V 1997, 'Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene', Circulation, vol. 96, no. 10, pp. 3570-3578.
Madeddu P, Varoni MV, Palomba D, Emanueli C, Demontis MP, Glorioso N et al. Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. Circulation. 1997 Nov 18;96(10):3570-3578.
Madeddu, Paolo ; Varoni, Maria Vittoria ; Palomba, Domenico ; Emanueli, Costanza ; Demontis, Maria Piera ; Glorioso, Nicola ; Dessì-Fulgheri, Paolo ; Sarzani, Riccardo ; Anania, Vittorio. / Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. In: Circulation. 1997 ; Vol. 96, No. 10. pp. 3570-3578.
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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.",
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AU - Emanueli, Costanza

AU - Demontis, Maria Piera

AU - Glorioso, Nicola

AU - Dessì-Fulgheri, Paolo

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N2 - 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.

AB - 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.

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