Bradykinin

How is bradykinin synthesized?

Bradykinin is formed from kininogen under the action of kallikrein.

• Kininogen is a precursor protein circulating in the blood.
• Kallikrein is an enzyme; in the kidneys, it is contained in the cells of the distal tubules.
• Bradykinin is an active peptide, the product of this reaction.

Physiological effects: what does bradykinin act on?

The peptide is involved in the regulation of hemodynamics and water-salt metabolism, ultimately leading to a decrease in blood pressure.

• Vascular effects: exerts a vasodilatory effect. It dilates small arterial vessels and precapillary sphincters, increases venous return, and enhances blood shunting into the venous bed through arteriovenous anastomoses. It alters tone and increases the permeability of vascular walls.
• Renal effects: increases renal blood flow and alters vascular permeability. It decreases the reabsorption of sodium ions ($Na^+$) in the tubules directly or via aldosterone suppression, and increases the urinary excretion of water, as well as $K^+$, $Na^+$, and $Cl^-$ ions.
• Neuropeptide effects: in experiments against the background of cycloheximide action, bradykinin restored a blocked defensive reflex.

Role in the pathogenesis of inflammation and pain

Bradykinin belongs to inflammatory mediators. Upon endothelial damage, such as by antigen-antibody complexes, the kinin-kallikrein system is activated.

• Exudation and thrombosis: due to increased vascular permeability, plasma enters the tissues. A decrease in plasma volume while maintaining the erythrocyte count leads to sludging, impaired hemorheological properties, and intravascular thrombosis. Bradykinin also affects the clotting and fibrinolytic systems.
• Cellular reactions: the peptide stimulates leukocyte chemotaxis, activates Hageman factor, collagenogenesis, and cyclooxygenase.
• Nociception: bradykinin acts as an activator of vanilloid receptors alongside protons, ATP, and vanilloids. It increases the sensitivity of pain receptors to external stimuli and in some cases, such as inflammation, can independently cause pain. Accumulation of bradykinin in tissues is listed among pain mediators during childbirth, while local manifestations in ARVI are due to inflammatory mediators, specifically bradykinins.

Clinical significance and pharmacology

• Iatrogenic cough and edema: ACE inhibitor therapy blocks the degradation of kinins. The accumulation of bradykinin in tissues is associated with dry cough and angioedema; cough caused by ACE inhibitors develops in 5–20% of patients.
• Reduced anesthesia efficacy: in the inflammation focus, bradykinin and other mediators lower the pain sensitivity threshold. Hyperemia, increased vascular permeability, and tissue edema promote rapid washout and dilution of the local anesthetic, reducing its activity.
• Amniotic fluid embolism: solid elements of amniotic fluid, including meconium and epithelial squames, irritate the interoceptors of pulmonary vessels. This causes a massive release of endogenous mediators, including bradykinin.
• Antitussive therapy: rengalin—a combination of antibodies to bradykinin, morphine, and histamine—can be used to treat dry, non-productive cough in community-acquired pneumonia.

Class and exam questions

What else to study on this topic

• Kinin-kallikrein system
• Nociception and pain mechanisms
• Blood pressure regulation
• Inflammatory mediators

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.