Bradykinin

Bradykinin is a biologically active oligopeptide with a molecular mass of about 1,000 daltons, consisting of 9 amino acids. The exact amino acid sequence is:

H2N-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-COOH. Bradykinin is released by the degradation of a high molecular weight kininogen by kallikreins. Bradykinin is involved in plasma extravasation, bronchoconstriction, nociception, vasodilation, and inflammation. It has an effect similar to histamine. It has a chemotactic effect on leukocytes and is a component of bee venom (see insect venom allergy below), among others.

Bradykinin mediates inflammation by causing vasodilation, increasing vascular permeability, and stimulating the synthesis of prostaglandins. Bradykinin causes pain by directly stimulating primary sensory neurons and causing the release of substance P, neurokinin, and calcitonin gene-related peptide. Its bronchoconstrictor action is associated with asthma and rhinitis. It increases renal blood flow by vasodilation and causes natriuresis by inhibiting sodium reabsorption. Bradykinin is degraded by peptidases.

Bradykinin develops its effects by binding to bradykinin receptors. This results primarily in the vasodilatory, antiproliferative, antihypertrophic, antifibrotic, antithrombotic, and antioxidant properties associated with the release of endothelial factors such as nitric oxide, prostacyclin, and tissue plasminogen activator.

Bradykinin is an oligopeptide with a molecular mass of about 1,000 daltons, consisting of 9 amino acids. The exact amino acid sequence is:

H2N-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-COOH.

Bradykinin is released by kininogenases such as kallikrein by proteolytic cleavage from its inactive precursor proteins, kininogens. In humans, bradykinin is degraded by three kininases:

• Angiotensin Converting Enzyme ( ACE)
• Aminopeptidase P (APP)
• Carboxypeptidase N (CPN).

Bradykinin is involved in allergic and anaphylactic reactions. It is essential mediator of angioedema and allergic reactions. Bradykinin is a potent endothelium-dependent vasodilator, causes contraction of non-vascular smooth muscle, increases vascular permeability, and is also involved in the pain mechanism. Bradykinin has an effect similar to histamine. It has a chemotactic effect on leukocytes and is, among other things, a component of bee venom (see below Insect venom allergy).

Bradykinin is thought to be responsible for the known side effects of ACE inhibitors such as cough, pruritus, urticaria, and angioedema.

In ACE inhibitor-induced angioedema, bradykinin degradation is impaired. Doubling of bradykinin levels in the blood may occur.

Dialysis: Bradykinin (BK) has been identified as a major mediator of hypersensitivity reactions in patients dialyzed with negatively charged membranes and concomitantly treated with angiotensin-converting enzyme (ACE) inhibitors.

1. Dendorfer A et al (2001) Pathways of bradykinin degradation in blood and plasma of normotensive and hypertensive rats. At J Physiol Heart Circ Physiol 280: 82-118
2. Graefe KH et al. (2016) Pharmaceuticals with an effect on the vascular system. In: Graefe KH et al. (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart p.171