Renovascular hypertension in bradykinin B2-receptor knockout mice

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.