What Is Bradykinin and What Does It Do?

Bradykinin is a peptide, or small protein, that functions as a signaling molecule within the body. As a member of the kinin family of proteins, its actions are diverse, influencing processes ranging from local blood flow to the sensation of pain.

The Bradykinin Lifecycle: Formation and Inactivation

The production of bradykinin is governed by the kallikrein-kinin system. This process begins when an enzyme called plasma kallikrein acts on a precursor molecule, high-molecular-weight kininogen (HMWK), to release the active bradykinin peptide. This system ensures bradykinin is produced precisely when needed, such as in response to tissue injury.

Once released, bradykinin has a short lifespan as its activity is rapidly terminated by enzymes. The primary enzyme for this inactivation is Angiotensin-Converting Enzyme (ACE), also known as kininase II, found in high concentrations in the lungs and kidneys. Other enzymes also help break down bradykinin, ensuring its effects are temporary and localized.

Key Functions of Bradykinin in the Body

Bradykinin has several key functions in the body:

• Vasodilation, the widening of blood vessels. It acts on the inner lining of blood vessels, prompting the release of substances that cause smooth muscle to relax. This leads to increased blood flow and a decrease in blood pressure.
• Increased vascular permeability, which makes capillaries “leakier.” This allows fluid and white blood cells to move into surrounding tissues, which is a necessary step in the healing process and a component of inflammation.
• Pain signaling. When tissues are damaged, bradykinin is released and sensitizes the endings of sensory nerves. It lowers the activation threshold of pain receptors, making the area more sensitive to stimuli.
• Contraction of non-vascular smooth muscles. This includes muscles in the bronchi, which can lead to bronchoconstriction, as well as in the gut and uterus, influencing processes from airway diameter to digestion.

Bradykinin Receptors: Gateways for Action

Bradykinin exerts its effects by binding to specific protein structures on cell surfaces known as bradykinin receptors. These receptors act as gateways, translating the external signal into an internal cellular response. There are two main types, the B1 receptor and the B2 receptor.

The B2 receptor is almost always present on various cells under normal conditions. This receptor is responsible for mediating most of bradykinin’s immediate effects. Actions such as rapid vasodilation and the immediate sensation of pain following an injury are triggered through B2 receptor activation.

In contrast, the B1 receptor is found at low levels in healthy tissues. Its production is significantly increased, or “upregulated,” in response to tissue injury or inflammation. The B1 receptor is therefore more involved in mediating sustained inflammatory responses and pain, making it a participant in chronic conditions.

When Bradykinin Contributes to Disease

Dysregulation of the bradykinin system can lead to disease. A primary example is Hereditary Angioedema (HAE), a genetic disorder characterized by recurrent, severe swelling. In HAE, defects in the proteins that control the kallikrein-kinin system lead to bradykinin overproduction. This excess increases vascular permeability, causing fluid to leak into tissues and resulting in swelling in the face, airways, and gastrointestinal tract.

Bradykinin also contributes to the symptoms of many inflammatory conditions. In chronic inflammatory diseases, its sustained presence contributes to persistent swelling, redness, and pain. Its role extends to some allergic reactions, where its release can exacerbate symptoms.

The molecule is also implicated in sepsis, a life-threatening response to infection. During sepsis, massive vasodilation and vascular leakage can lead to a catastrophic drop in blood pressure, known as septic shock. A “bradykinin storm” has also been proposed as a contributor to the symptoms and complications seen in some patients with COVID-19.

Medical Approaches Targeting Bradykinin

Understanding bradykinin has enabled the development of targeted medical therapies. One class of drugs, Angiotensin-Converting Enzyme (ACE) inhibitors, is used to treat high blood pressure by blocking the ACE enzyme. This action slows the breakdown of bradykinin, and the resulting increase in its levels contributes to the blood pressure-lowering effect through vasodilation.

The accumulation of bradykinin from ACE inhibitors can also cause side effects, the most common being a persistent dry cough. In rare cases, this buildup can lead to angioedema, a condition of severe swelling similar to that seen in HAE.

For diseases caused by bradykinin overproduction, such as HAE, more specific treatments exist. Bradykinin receptor antagonists, like the drug icatibant, work by directly blocking the B2 receptor to prevent swelling. Other therapies, known as kallikrein inhibitors, target the enzyme that produces bradykinin, thereby reducing its overall levels.