Endogenous kinins are important vasoactive peptides whose actions are mediated by G protein-coupled receptors (R), B2R (constitutive) and B1R (inducible). They are involved in vascular homeostasis, ischemic pre- and post-treatment, and cardiovascular disease and contribute to the therapeutic effects of angiotensin-1 converting enzyme inhibitors (ACEIs) and angiotensin AT1 receptor blockers.
The action of bradykinin receptors results primarily in vasodilator, antiproliferative, antihypertrophic, antifibrotic, antithrombotic, and antioxidant properties associated with the release of endothelial factors such as nitric oxide, prostacyclin, and tissue plasminogen activator.
Uncontrolled production of kinins or inhibition of their metabolism may lead to undesirable proinflammatory side effects. Therefore, B2R antagonism is beneficial in angioedema (effect of icatibant), septic shock, stroke, and Chagas vasculopathy.
B1R is virtually absent in healthy tissue, but this receptor is induced by the cytokine pathway and oxidative stress via the transcriptional nuclear factor NF-κB. Activation of both receptors is particularly observed in neovascularization, angiogenesis, cardiac ischemia, and diabetic nephropathy.
At the same time, B1R is a potent activator of inducible nitric oxide and NADPH oxidase, which have been associated with vascular inflammation, increased permeability, insulin resistance, endothelial dysfunction, and diabetic complications (Couture R et al. 2014).