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Bradykinin

Bradykinin is an endogenous vasodilator nonapeptide, (formed of nine amino acid residues), released from plasma globulins called kininogens. There are two kininogens, a high molecular weight (HMW) form present in plasma and a low molecular weight (LMW) form present in tissues.

Metabolism

HMW kininogen is synthetized in the liver and released into plasma. Hydrolysis of plasma kininogen, catalyzed by plasma kallikrein, a protease, gives bradykinin whose half-life in plasma is less than one minute. There are plasma and tissue kallikreins. The hydrolysis of LMW kininogen by tissue kallikrein gives kallidin, a vasodilator decapeptide whose properties are quite similar to those of bradykinin.

Effects

Bradykinin effects result from stimulation of B1 and B2 receptors (must be differentiated from beta adrenergic receptors):

Cardiovascular action

  • Vasodilation:
    Bradykinin is one of the most powerful known vasodilators. Its vasodilatator and hypotensive effects resulting from B2 receptor stimulation are, at least partially, the consequence of nitric oxide release. Vasodilation is particularly marked in capillaries.
  • Increase in capillary permeability:
    Bradykinin increases capillary permeability and induces edema.
    It reproduces symptoms of inflammation and has an algesic action (B2 effect).
  • Cardiac stimulation:
    The fall of arterial pressure is accompanied by tachycardia and increase in cardiac output. The cardiac effects are explained by an indirect action (release of catecholamines during hypotension) but also by a direct action, bradykinin accelerates and reinforces cardiac contractions. It elicits also a coronary vasodilation.

Bradykinin, perhaps by release of nitric oxide and PGI2 prostaglandin, has a cardiac anti-ischemic effect, inhibited by B2 antagonists

Action on smooth muscles

The action of bradykinin differs according to organs and species. On the isolated ileum of guinea-pig for example, bradykinin induces a slow contraction (explaining the origin of the word bradykinin) of long duration. Bradykinin elicits bronchoconstriction in most species and could be involved in certain asthma and coughs.

Other actions

Bradykinin stimulates the release of antidiuretic hormone and has, under certain conditions, a natriuretic action.

It causes hyperemia of salivary glands.
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