Bradykinin deficiency causes high blood pressure in mice

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 BK^delK1 and BK^delK2 mutant mice, targeting the BK portion of mouse kininogen1 and kininogen2 genes, respectively. The BK^delK1 and BK^delK2 mutant mice had about 50% reductions in plasma low molecular weight kininogen and trypsin-released BK, compared to wild mice. Both BK^delK1 and BK^delK2 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.