From the Guidelines
Bradykinin is a peptide hormone that acts as a powerful vasodilator in the human body, playing a crucial role in regulating blood pressure, fluid balance, and pain sensation, and is involved in pathological conditions like angioedema. It consists of nine amino acids and belongs to the kinin family of proteins. Bradykinin is produced naturally through the kallikrein-kinin system when tissue damage, inflammation, or allergic reactions occur. Its primary functions include causing blood vessels to dilate (widen), increasing vascular permeability, stimulating pain receptors, and promoting inflammation as part of the body's natural immune response. Bradykinin works by binding to specific receptors called B1 and B2 receptors on cell surfaces, triggering a cascade of cellular responses. This peptide plays important roles in regulating blood pressure, fluid balance, and pain sensation. It's also involved in certain pathological conditions like angioedema, where excessive bradykinin production leads to swelling of tissues. Some medications, particularly ACE inhibitors used to treat hypertension, can increase bradykinin levels by preventing its breakdown, which explains side effects like dry cough associated with these drugs, as noted in studies such as 1 and 1.
Key Points
- Bradykinin is a peptide hormone with vasodilatory effects
- It is involved in the regulation of blood pressure, fluid balance, and pain sensation
- Excessive bradykinin production can lead to angioedema
- ACE inhibitors can increase bradykinin levels, leading to side effects like dry cough
- The most recent guidelines, such as those from 1, emphasize the importance of considering bradykinin's role in angioedema when using ACE inhibitors.
Mechanism of Action
Bradykinin's mechanism of action involves binding to B1 and B2 receptors on cell surfaces, triggering a cascade of cellular responses that lead to vasodilation, increased vascular permeability, and stimulation of pain receptors. This is supported by studies such as 1, which highlight the role of bradykinin in enhancing vascular permeability.
Clinical Implications
The clinical implications of bradykinin's effects are significant, particularly in the context of ACE inhibitor use. As noted in 1 and 1, ACE inhibitors can increase bradykinin levels, leading to side effects like dry cough and angioedema. Therefore, it is essential to carefully consider the potential risks and benefits of ACE inhibitor therapy in patients with a history of angioedema or other conditions that may be exacerbated by increased bradykinin levels.
From the Research
Definition and Function of Bradykinin
- Bradykinin is a potent vasodilating and natriuretic peptide 2
- It plays a role in lowering blood pressure by reducing total peripheral vascular resistance in a dose-dependent manner 2
- Bradykinin is formed by the interaction of factor XII, prekallikrein, and high-molecular-weight kininogen on negatively charged surfaces or macromolecular organic surfaces 3
- It is degraded by carboxypeptidase N and angiotensin-converting enzyme 3
Role in Angioedema and Inflammatory Disease
- Angioedema that is bradykinin dependent results from hereditary or acquired C1 inhibitor deficiencies or use of angiotensin-converting enzyme inhibitors 3
- Bradykinin contributes to tissue hyperresponsiveness, local inflammation, and hypotension in allergic rhinitis, asthma, and anaphylaxis 3
- An increase in bradykinin levels results in continued prostaglandin E2 synthesis, vasodilation, increased vascular permeability, and increased interstitial fluid 4
Interaction with Other Vasoactive Factors
- Both bradykinin B1 and B2 receptors participate in the maintenance of normal vasoregulation or development of hypertension 5
- Blockade of bradykinin receptors leads to upregulation of genes of related vasoactive systems, including eNOS, AT1 receptor, PGE2 receptor, and tissue kallikrein 5
- Angiotensin-converting enzyme inhibitors potentiate the effects of bradykinin, which may play an important role in the blood pressure lowering effect of these inhibitors 2