Bradykinin-bradykinin 2 receptor and oxidative stress

Bradykinin (BK) and its primary receptor, the bradykinin 2 receptor (B2R), play pivotal roles in regulating oxidative stress. While B2R activation has traditionally been linked to elevated reactive oxygen species (ROS) and pro-apoptotic signalling, growing evidence indicates that, under specific contexts, it also exerts antioxidative and cytoprotective effects, enhancing cell survival, promoting proliferation and attenuating apoptosis.

We retrieved data from electronic databases PubMed, Web of Science, and ScienceDirect to systematically evaluate the bidirectional redox regulation mediated by B2R and propose a dynamic model that reconcile this apparent paradox.

Our analysis underscores a tight association between the oxidative outcome of BK-B2R signalling and the duration of stimulation: multiple independent studies, together with our time-stratified analyses, suggest that prolonged BK exposure is more likely to elicit antioxidative responses. Mechanistically, an early, transient rise in ROS may activate cascades such as mitogen-activated protein kinase (MAPK), subsequently inducing adaptive antioxidant defences (e.g. catalase upregulation), thereby reframing 'controlled' ROS not as a purely toxic byproduct but as a signalling cue that sustains redox homeostasis.

In sum, B2R is not a unidirectional pro-oxidant or antioxidant factor; rather, it functions as a context- and time-dependent modulator of oxidative stress. This refined understanding provides a conceptual framework for stage- or condition-specific B2R-targeted interventions in cardiovascular, neurological and inflammation-related disorders.