4.6 Article

Bradykinin deficiency causes high blood pressure in mice

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Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2023.09.059

Keywords

Bradykinin; Kininogen; Mutant mice; Systolic blood pressure; Low-molecular weight kininogen

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Bradykinin plays various physiological roles, including vasodilation and blood pressure reduction. Mutant mice experiments indicated that plasma LKNG is the source of KNG in the vascular kallikrein-kinin system, and it contributes significantly to maintaining lower systolic blood pressure.
Bradykinin has a wide variety of physiological functions, including vasodilation and blood pressure reduction. However, the physiological roles of bradykinin are not fully understood. We used the CRISPR/Cas9 method to generate BKdelK1 and BKdelK2 mutant mice, targeting the BK portion of mouse kininogen1 and kininogen2 genes, respectively. The BKdelK1 and BKdelK2 mutant mice had about 50% reductions in plasma low molecular weight kininogen and trypsin-released BK, compared to wild mice. Both BKdelK1 and BKdelK2 mice had significantly elevated systolic blood pressure compared to WT mice. These results suggest that plasma LKNG is a source of KNG in the vascular kallikrein-kinin system and contributes to maintaining lower systolic blood pressure.

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