Bradykinin

Bradykinin helps histamine trigger acute inflammation – following injury, coagulation factor 12 is activated by the exposed collagen in the vessel wall, that initiates the Kinin-kallikrein pathway that creates Bradykinin, which plays an important role in pain. It also has some action in arteriole dilation and increase in venule permeability.

Angiotensin inhibitors increase bradykinin and can cause cough, angioedema and vasodilation.

Videos

Bradykinin Induced Vasodilation Part 1

Bradykinin Induced Vasodilation Part 2

Bradykinin Induced Vasodilation Part 3

Bradykinin Induced Vasodilation Part 4

Bradykinin Induced Vasodilation Part 5

Bradykinin Induced Vasodilation Part 6

Bradykinin Induced Vasodilation Part 7

Bradykinin Induced Vasodilation Part 8

Bradykinin Induced Vasodilation Part 9

Bradykinin Induced Vasodilation Part 10

Bradykinin Induced Vasodilation Part 11

Understanding Bradykinin

Bradykinin is a fascinating peptide that plays a crucial role in various physiological and pathological processes within the human body. It is a part of the kinin-kallikrein system, which is involved in inflammation, blood pressure regulation, and pain mediation. This note aims to provide a comprehensive overview of bradykinin, its functions, mechanisms, and its significance in health and disease.

What is Bradykinin?

Bradykinin is a nonapeptide, meaning it is composed of nine amino acids. It is produced from kininogen, a precursor protein, through the action of enzymes known as kallikreins. Bradykinin is a potent vasodilator, which means it can widen blood vessels, leading to a decrease in blood pressure. It is also known for its ability to increase vascular permeability, allowing substances to pass more easily through blood vessel walls.

Mechanism of Action

Bradykinin exerts its effects primarily through two types of receptors: B1 and B2 receptors. These receptors are part of the G-protein-coupled receptor family and are distributed throughout various tissues in the body.

B2 Receptors

• Constitutive Expression: B2 receptors are constitutively expressed, meaning they are always present in tissues.
• Vasodilation: Activation of B2 receptors by bradykinin leads to the production of nitric oxide and prostacyclin, both of which contribute to vasodilation.
• Pain and Inflammation: B2 receptor activation is also associated with the sensation of pain and the inflammatory response.

B1 Receptors

• Inducible Expression: B1 receptors are not usually present under normal conditions but are induced during tissue injury or inflammation.
• Chronic Inflammation: They play a significant role in chronic inflammatory conditions and are involved in the prolonged effects of bradykinin.

Physiological Roles

Bradykinin is involved in several key physiological processes:

1. Regulation of Blood Pressure: By causing vasodilation, bradykinin helps to lower blood pressure. It counteracts the effects of vasoconstrictors like angiotensin II.

2. Inflammatory Response: Bradykinin increases vascular permeability, allowing immune cells and proteins to reach sites of injury or infection more effectively.

3. Pain Sensation: It is known to sensitize nerve endings, contributing to the sensation of pain, particularly in inflammatory conditions.

4. Renal Function: Bradykinin plays a role in kidney function by influencing blood flow and sodium excretion.

Bradykinin in Disease

While bradykinin is essential for normal physiological functions, its dysregulation can contribute to various diseases:

Hereditary Angioedema (HAE)

• Cause: HAE is a genetic disorder characterized by recurrent episodes of severe swelling. It is often caused by a deficiency or dysfunction of C1 inhibitor, a protein that regulates the kinin-kallikrein system.
• Role of Bradykinin: Excessive bradykinin production leads to increased vascular permeability and the characteristic swelling seen in HAE.

Hypertension

• Protective Role: Bradykinin's vasodilatory effects can help counteract high blood pressure. However, its role in hypertension is complex and not fully understood.

Chronic Pain and Inflammation

• Contribution to Pain: Bradykinin is involved in the development of chronic pain conditions due to its ability to sensitize pain receptors.
• Inflammatory Diseases: It plays a role in diseases such as rheumatoid arthritis and inflammatory bowel disease.

Therapeutic Implications

Understanding the role of bradykinin has led to the development of various therapeutic strategies:

• ACE Inhibitors: These drugs, commonly used to treat hypertension, increase bradykinin levels by inhibiting its breakdown, thereby enhancing its vasodilatory effects.
• Bradykinin Receptor Antagonists: These are being explored as potential treatments for conditions like hereditary angioedema and chronic pain.