In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 3 ( 1998-09), p. 503-509
Abstract:
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) B 2 receptor in the contralateral kidney. BK B 2 -receptor knockout (B 2 −/− ), wild-type (B 2 +/+ ), and heterozygous (B 2 +/− ) 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 B 2 −/− mice than in B 2 +/− or B 2 +/+ 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 B 2 −/− mice than in B 2 +/− or B 2 +/+ 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 B 2 receptor by Icatibant enhanced the pressure response to clipping in B 2 +/+ 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 B 2 −/− mice (32 and 38 mm Hg, at 2 and 4 weeks, respectively), and higher in B 2 +/+ mice given Icatibant (30 and 32 mm Hg) than in B 2 +/+ 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 B 2 −/− and B 2 +/− mice, but this effect was delayed in B 2 +/+ mice. However, the HR response to clipping in B 2 +/+ 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 (B 2 −/− : 5.7±0.1 versus 5.2±0.1; B 2 +/+ : 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 B 2 receptor exert a protective action against excessive blood pressure elevation during early phases of 2K1C hypertension.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.32.3.503
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1998
detail.hit.zdb_id:
2094210-2
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