Renovascular hypertension in bradykinin B2-receptor knockout mice

Paolo Madeddu, Anna Franca Milia, Maria Bonaria Salis, Leonardo Gaspa, Wolkmar Gross, Andrea Lippoldt, Costanza Emanueli

Research output: Contribution to journalArticlepeer-review

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; P2(-/-) mice than in B2(+/-) or B2(+/+) mice (28±2 versus 14±2 and 14±2 mm Hg, respectively, at 2 weeks; P2 receptor by Icatibant enhanced the pressure response to clipping in B2(+/+) mice (29±2 mmHg 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 I 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; P2 receptor exert a protective action against excessive blood pressure elevation during early phases of 2K1C hypertension.

Original languageEnglish
Pages (from-to)503-509
Number of pages7
JournalHypertension
Volume32
Issue number3
Publication statusPublished - Sep 1998

Keywords

  • Angiotensin
  • Hypertension, renovascular
  • Hypertrophy, myocardial
  • Kallikrein-kinin system
  • Mice, kinin B-receptor, knockout

ASJC Scopus subject areas

  • Internal Medicine

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