The renal kallikrein-kinin system is activated under conditions of mineralocorticoid excess. To evaluate whether endogenous @entity69556 exert a protective role against the development of mineralocorticoid-induced @entity101 , we studied the cardiovascular effects induced by long-term administration of @entity8147 ( @entity4420 ; 0.3 micromol/g body wt s.c. once per week for 6 weeks) or vehicle in @entity19 ( @entity15347 -/-) lacking the bradykinin B2 receptor gene and in wild-type controls ( @entity15347 +/+). Under basal conditions, @entity15347 -/- @entity19 showed higher systolic blood pressure (tail-cuff plethysmography) than wild-type @entity15347 +/+ and heterozygous @entity15347 +/- @entity19 (121+/-2 versus 114+/-2 and 115+/-2 mm Hg, respectively; P<0.05 for both comparisons). Heart rate was higher in @entity15347 -/- and @entity15347 +/- than in @entity15347 +/+ (459+/-12 and 418+/-7 versus 390+/-7 bpm; P<0.05 for both comparisons). Systolic blood pressure was increased by @entity4420 in transgenic as well as in wild-type @entity19 , whereas no change was induced by the vehicle. The pressor response to @entity4420 was more rapid and pronounced in @entity15347 -/- than in @entity15347 +/+ and @entity15347 +/- (30+/-5 versus 15+/-4 and 6+/-3 mm Hg, respectively, at 3 weeks; P<0.01 for both comparisons). The difference in systolic blood pressure was consistent with that detected by direct intra-arterial measurements of mean blood pressure. Neither @entity4420 nor its vehicle altered heart rate or gain in body weight over time. Under basal conditions, urinary @entity1372 excretion did not differ between strains. During @entity4420 administration, cumulative urinary @entity1372 excretion was lower in @entity15347 -/- than in @entity15347 +/+ (2.59+/-0.15 versus 3.31+/-0.22 mmol, respectively, during the first week; P<0.05). Urinary kinin excretion was increased by @entity4420 in both @entity15347 -/- (from 0.65+/-0.17 to 4.27+/-0.80 pmol/24 h; P<0.01) and @entity15347 +/+ (from 0.55+/-0.09 to 6.27+/-1.48 pmol/24 h; P<0.05). The increase in urinary kinin excretion was similar between strains. These results show that integrity of the bradykinin B2 receptor is essential for regulation of blood pressure and heart rate under basal conditions. In addition, they indicate that activation of the kallikrein-kinin system represents a compensatory response against the development of @entity101 induced by mineralocorticoid excess.

Enhanced blood pressure sensitivity to @entity8147 in XXXX with disruption of bradykinin B2 receptor gene.

@entity15347 :: ('12062(Tax:10090)', 'Gene') :: ['Bk2r'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity8147 :: ('MESH:D003900', 'Chemical') :: ['deoxycorticosterone'] @entity4420 :: ('CHEBI:16973', 'Chemical') :: ['DOC'] @entity69556 :: ('MESH:D007705', 'Chemical') :: ['kinins']
@entity19 :: (10090,Species) :: ['mice']
