The effects of natriuretic peptides on the bradykinin signaling pathway after ischemic mouse brain injury

Among the consequences of a stroke are brain edemas, which additionally increase brain damage. This study is focused on cerebral edemas and bradykinin as their direct cause. It is known that natriuretic peptides decrease cerebral edema after ischemic brain injury through mechanisms that are still unknown. We examined the effects of natriuretic peptides and the bradykinin signaling pathway in vitro in HEK293 cells, primary isolated neurons, and astrocytes using the whole cell patch clamp technique and by measuring the intracellular calcium concentration. In a mouse model of ischemic brain injury (MCAO), we determined the degree of neurological damage in the mouse brain in vivo after applying only bradykinin or a combination of bradykinin with natriuretic peptides. We measured the size of the ischemic lesion and edema by micro CT and performed histological staining by Nissl. In HEK293 cells, ligands of guanylat cycalse A, but not guanylat cyclase B, inhibited the bradykinin signaling pathway (bradykinin receptor type 2-dependent). Our preliminary results showed that the same inhibition exists in primary isolated mouse neurons. When natriuretic peptides were applied, no brain damage was detected. As shown in our previous study, when only bradykinin was applied, brain damage increased in comparison to control animals through an increase in the brain edema. However, the combination with natriuretic peptides decreased the size of the lesion and the brain edema. The results indicate the existence of an endogenous antagonist of the bradykinin signaling pathway and a possible protective role for natriuretic peptides in humans during strokes.