Bradykinin is a naturally occurring peptide, a small protein-like molecule, produced within the human body. It functions as a potent mediator in various physiological processes. Found in the blood and tissues, this compound plays a significant role in how the body responds to different stimuli.
Primary Actions in the Body
Bradykinin exerts its influence primarily by interacting with B2 receptors on cell surfaces. One of its most well-understood actions is vasodilation, the widening of blood vessels. This increases blood flow to the affected area, a process that can help deliver immune cells and nutrients.
It also increases vascular permeability, making blood vessel walls more porous. This allows fluids and immune cells to move from the bloodstream into surrounding tissues. This increased permeability is a characteristic feature of inflammation, contributing to swelling and redness.
Bradykinin also contributes to pain. It does this by activating nerve endings, signaling tissue damage or irritation.
Involvement in Health Conditions
The actions of bradykinin are implicated in several health conditions. In hereditary angioedema (HAE), a rare genetic disorder, an uncontrolled increase in bradykinin levels leads to recurrent episodes of severe swelling. This swelling can affect various body parts, including the face, airways, and gastrointestinal tract, and is caused by a deficiency or dysfunction of C1 esterase inhibitor, which normally helps regulate bradykinin production.
Bradykinin also contributes to the cough experienced by some individuals taking angiotensin-converting enzyme (ACE) inhibitor medications, commonly prescribed for high blood pressure. When ACE is inhibited, bradykinin accumulates, leading to irritation of the airways and a persistent dry cough.
How the Body Regulates It
The body controls bradykinin levels through the kinin-kallikrein system. This system involves enzymes that produce bradykinin from precursor proteins called kininogens. For example, plasma kallikrein cleaves high molecular weight kininogen to release bradykinin.
Once produced, enzymes break down bradykinin to prevent excessive accumulation. Angiotensin-converting enzyme (ACE) is a primary enzyme in this degradation. Aminopeptidase P (APP) also contributes to bradykinin inactivation. This balance of production and breakdown ensures bradykinin’s effects are localized and transient, preventing overactivity.
Targeting Bradykinin for Treatment
Understanding bradykinin’s mechanisms has opened avenues for treatment. For instance, in hereditary angioedema, medications like icatibant manage acute attacks by selectively blocking the bradykinin B2 receptor, preventing its effects and reducing swelling.
Other approaches target enzymes that regulate bradykinin. While ACE inhibitors can increase bradykinin levels and cause side effects, their primary therapeutic action relates to the renin-angiotensin system. Research continues to explore ways to modulate bradykinin pathways for various conditions, aiming to harness beneficial effects while mitigating unwanted ones.