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Renovascular hypertension in bradykinin B2-receptor knockout mice

Madeddu, Paolo Roberto and Milia, Anna Franca and Salis, Maria Bonaria and Gaspa, Leonardo and Gross, Wolkmar and Lippoldt, Andrea and Emanueli, Costanza (1998) Renovascular hypertension in bradykinin B2-receptor knockout mice. Hypertension, Vol. 32 (3), p. 503-509. eISSN 1524-4563. Article.

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Abstract

We evaluated whether kinins exert a protective action against the development of two-kidney, one clip (2K1C) hypertension, a model characterized by an activated renin-angiotensin system in the ischemic kidney and increased expression of the bradykinin (BK) B2 receptor in the contralateral kidney. BK B2-receptor knockout (B2 -/-), wild-type (B2 +/+), and heterozygous (B2 +/-) mice underwent clipping of the left renal artery, with the other kidney remaining untouched. Basal systolic blood pressure (SBP, via tail-cuff plethysmography) was higher in B2 -/-mice than in B2 +/- or B2 +/+ mice (121±2 versus 113±2 and 109±1 mm Hg; P<0.05 for both comparisons). SBP did not change from basal values after sham operation, but it increased in mice that underwent clipping. The increase in SBP was greater in 2K1C B2 -/- mice than in B2 +/- or B2 +/+ mice (28±2 versus 14±2 and 14±2 mm Hg, respectively, at 2 weeks; P<0.05 for both comparisons). Blockade of the BK B2 receptor by Icatibant enhanced the pressure response to clipping in B2 +/+ mice (29±2 mm Hg at 2 weeks). Intra-arterial mean blood pressure (MBP) was higher in 2K1C than in respective sham-operated mice, with the MBP difference being higher in B2 -/- mice (32 and 38 mm Hg, at 2 and 4 weeks, respectively), and higher in B2 +/+ mice given Icatibant (30 and 32 mm Hg) than in B2 +/+ mice without Icatibant (17 and 18 mm Hg). At 4 weeks, acute injection of an angiotensin type 1 receptor antagonist normalized the MBP of 2K1C hypertensive mice. A tachycardic response was observed 1 week after clipping in B2 -/- and B2 +/- mice, but this effect was delayed in B2 +/+ mice. However, the HR response to clipping in B2 +/+ mice was enhanced by Icatibant. Within each strain, heart weight to body weight ratio was greater in 2K1C hypertensive mice than in sham-operated control animals (B2 -/-: 5.7±0.1 versus 5.2±0.1; B2 +/+: 5.1±0.1 versus 4.5±0.1; P<0.01 for both comparisons). The clipped kidney weight to nonclipped kidney weight ratio was consistently reduced in mice with 2K1C hypertension. Our results indicate that kinins acting on the BK B2 receptor exert a protective action against excessive blood pressure elevation during early phases of 2K1C hypertension.

Item Type:Article
ID Code:870
Status:Published
Refereed:Yes
Uncontrolled Keywords:Angiotensin, renovascular hypertension, kinin B2-receptor knockout mice, myocardial hypertrophy, kallikrein-kinin system
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
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:1524-4563
Copyright Holders:© 1998 American Heart Association
Deposited On:18 Aug 2009 10:03

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