BLOOD-PRESSURE RESPONSES TO ACUTE OR CHRONIC CAPTOPRIL IN MICE WITH DISRUPTION OF BRADYKININ B-2-RECEPTOR GENE

Objective To evaluate the role of kinins in the hypotensive response t o angiotensin converting enzyme inhibition, we compared the blood pres sure effects induced by acute or chronic captopril administration in a mouse strain (Bk2r(-/-)) with disruption of the bradykinin B-2 recept or gene and in wild-type controls (J129 Sv mice). A second aim was to determine whether Icatibant, a selective bradykinin B-2-receptor antag onist, prevented the blood pressure changes induced by acute captopril administration in Swiss, c57/B16, J129 Sv and Bk2r(-/-) mice. Methods and results Under basal conditions, tail-cuff systolic blood pressure (SBP) and intra-arterial mean blood pressure (MBP) were higher in Bk2 r(-/-) than in J129 Sv (SBP: 132 +/- 2 versus 113 +/- 3 mmHg; MBP: 144 +/- 6 versus 122 +/- 10 mmHg, P < 0.05 for both comparisons). Acute c aptopril administration (1 mg/kg body weight, intra-arterially) reduce d the MBP of Bk2r(-/-) and J129 Sv by 36 +/- 8 and 31 +/- 7 mmHg, resp ectively. Swiss and c57/B16 mice showed similar decreases in MBP follo wing captopril. Pretreatment with Icatibant (10 nmol/kg body weight, i ntra-arterially) did not influence the MBP responses to acute captopri l in all the strains. Chronic administration of captopril (approximate ly 120 mg/kg body weight per day for 2 weeks in drinking water) reduce d SBP in either Bk2r(-/-) or J129 Sv. The magnitude of this response w as higher in Bk2r(-/-) than in J129 Sv (65 +/- 3 versus 47 +/- 4 mmHg, respectively, P < 0.01). Conclusions Our results suggest that endogen ous kinins do not participate in the hypotensive response to angiotens in converting enzyme inhibition in mice; in Bk2r(-/-), the exaggerated blood pressure response to chronic captopril appears to be attributab le to interference with unbalanced vasoconstrictor action of the renin -angiotensin system. (C) Rapid Science Publishers ISSN 0263-6352.