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

Madeddu, Paolo Roberto and Varoni, Maria Vittoria and Palomba, Domenico and Emanueli, Costanza and Demontis, Maria Piera and Glorioso, Nicola and Dessì-Fulgheri, Paolo Lorenzo Giuseppe and Sarzani, Riccardo and Anania, Vittorio Domenico (1997) Cardiovascular phenotype of a mouse strain with disruption of bradykinin B2-receptor gene. Circulation, Vol. 96 (10), p. 3570-3578. eISSN 1524-4539. Article.

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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; P<.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r-/- than in Bk2r+/+ and Bk2r+/- mice (505±10 versus 449±12 and 477±10 mg/100 g body wt, P<.05). Chronic blockade of B2-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 AT1-receptor antagonist reduced the basal blood pressure of Bk2r-/- by 21±3 mm Hg (P<.05) to the levels of Bk2r+/+. No difference was detected between strains as far as plasma renin activity and the expression of renin and AT1-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.

Item Type:Article
ID Code:3995
Status:Published
Refereed:Yes
Uncontrolled Keywords:Kinins, bradykinin, receptors, genes
Subjects:Area 07 - Scienze agrarie e veterinarie > VET/07 Farmacologia e tossicologia veterinaria
Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
001 Università di Sassari > 01 Dipartimenti > Biologia animale
002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo
Publisher:Lippincott Williams & Wilkins
eISSN:1524-4539
Copyright Holders:© 1997 American Heart Association
Deposited On:10 Jun 2010 19:05

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