Background To evaluate the role of kinins in the regulation of cardiovascular function, we studied the phenotype of a mouse strain with disruption of the bradykinin B₂-receptor gene (Bk 2r^−/−).

Methods and Results Under basal conditions, tail-cuff blood pressure was higher in Bk2r^−/− than in wild-type Bk2r^+/+ and heterozygous Bk2r^+/− mice (124±1 versus 109±1 and 111±2 mm Hg, respectively; P<.01 for both comparisons), a difference that was confirmed by measurements of intra-arterial blood pressure in unanesthetized mice. Heart weight was greater in Bk2r^−/− than in Bk2r^+/+ and Bk2r^+/− mice (505±10 versus 449±12 and 477±10 mg/100 g body wt, P<.05). Chronic blockade of B₂-receptors by Icatibant (50 nmol/100 g body wt twice a day SC) or inhibition of nitric oxide synthase by nitro-l-arginine-methyl ester (0.14 mmol/100 g body wt orally) increased the blood pressure of Bk2r^+/+ to the levels of Bk2r^−/− mice. Compared with the wild-type strain, both Bk2r^−/− and Bk2r^+/− mice showed exaggerated vasopressor responses to angiotensin II. In addition, chronic administration of an angiotensin AT₁-receptor antagonist reduced the basal blood pressure of Bk2r^−/− by 21±3 mm Hg (P<.05) to the levels of Bk2r^+/+. No difference was detected between strains as far as plasma renin activity and the expression of renin and AT₁-receptor genes are concerned. Chronic salt loading (0.84 mmol/g chow for 15 days) increased the blood pressure of Bk2r^−/− and Bk2r^+/− by 34±3 and 14±6 mm Hg, respectively, whereas it was ineffective in Bk2r^+/+.

Conclusions Our results suggest that a normally functioning B₂-receptor is essential for the maintenance of cardiovascular homeostasis in mice. Dysfunction of the kallikrein-kinin system could contribute to increase blood pressure levels by leaving the activity of vasoconstrictor agents unbalanced.