Bradykinin is a peptide, a small protein-like molecule, that participates in various bodily functions. As a component of the kinin group of proteins, it has a role in managing inflammation. This molecule is an operator in systems that control blood flow and the body’s response to injury.
Formation and Breakdown of Bradykinin
Bradykinin is a product of the kinin-kallikrein system, a complex cascade activated in response to tissue damage. The process begins with a precursor molecule called high-molecular-weight kininogen (HMWK). An enzyme named kallikrein acts on HMWK, cleaving it to release the active bradykinin peptide. This formation occurs in various tissues and fluids throughout the body.
Once formed, bradykinin has a very short lifespan, often lasting only for seconds in the bloodstream. Its rapid inactivation is carried out by an enzyme called Angiotensin-Converting Enzyme (ACE), also known as kininase II. ACE is abundant in the lungs and kidneys and breaks down bradykinin into inactive fragments. This quick degradation is a control mechanism, preventing its effects from becoming widespread and prolonged.
Physiological Roles in the Body
A primary function of bradykinin is to widen blood vessels, a process called vasodilation. It acts on the endothelial cells that line blood vessels, prompting them to release substances like nitric oxide and prostacyclin. These substances then signal the smooth muscle cells in the vessel walls to relax, increasing the vessel’s diameter. This action helps to lower blood pressure and increase blood flow to tissues.
Bradykinin also plays a part in the inflammatory response. It increases vascular permeability, which makes the walls of small blood vessels leakier. This allows fluid, plasma proteins, and immune cells to move from the bloodstream into surrounding tissues. This leakage contributes to the swelling, or edema, that is a characteristic of inflammation.
Bradykinin is also directly involved in the sensation of pain. When tissues are damaged, bradykinin is released and stimulates specialized nerve endings called nociceptors. It can sensitize these nerve endings, making them more responsive to other painful stimuli. This action signals that an injury has occurred, contributing to the pain that encourages protection of the affected area.
Involvement in Medical Conditions
Faulty bradykinin regulation can lead to significant medical issues. A primary example is Hereditary Angioedema (HAE), a genetic disorder characterized by recurrent, severe swelling. In individuals with HAE, there is often a deficiency of the C1 esterase inhibitor protein, which helps control the kinin-kallikrein system. Without this inhibitor, excessive bradykinin production leads to increased vascular permeability and episodes of swelling in the skin, airways, and gastrointestinal tract.
Bradykinin’s effects are also seen in acute allergic responses. During anaphylaxis, various inflammatory mediators are released, and bradykinin can be involved. Its ability to cause vasodilation and increase vascular permeability contributes to the rapid drop in blood pressure and swelling during these reactions. The peptide’s actions compound the effects of other molecules like histamine.
Connection to Common Medications
Bradykinin’s interaction with certain medications highlights its clinical relevance. Angiotensin-Converting Enzyme (ACE) inhibitors, such as lisinopril and enalapril, are drugs prescribed to manage high blood pressure and heart failure. These medications work by blocking the ACE enzyme, which prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby lowering blood pressure.
A direct consequence of inhibiting ACE is the reduced breakdown of bradykinin. This leads to higher levels of the peptide in the body, which contributes to the blood pressure-lowering effect of ACE inhibitors through its vasodilatory properties.
This increase in bradykinin is also responsible for a common side effect of ACE inhibitors: a persistent dry cough. Elevated bradykinin levels in the lungs are thought to sensitize nerve fibers, triggering the cough reflex. In rare instances, this buildup can lead to drug-induced angioedema, which involves swelling similar to HAE.