Bradykinin-bradykinin 2 receptor and oxidative stress.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.