Chapter: Modern Pharmacology with Clinical Applications: The Renin–Angiotensin– Aldosterone System and Other Vasoactive Substances

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Bradykinin

The kallikrein–kinin system is an enzymatic pathway giving rise to two predominant vasoactive peptides, kallidin and bradykinin.

Bradykinin

The kallikrein–kinin system is an enzymatic pathway giving rise to two predominant vasoactive peptides, kallidin and bradykinin. Kallikrein, the enzyme respon-sible for the formation of these peptides, exists in plasma and tissues. However, circulating levels of the end products, kallidin and bradykinin, are quite low be-cause the kallikrein enzymes are present largely in in-active forms. In addition, the short half-life of these pep-tides (15 seconds) also contributes to low plasma levels. In general, the kinins produce relaxation of vascular smooth muscle and vasodilation. Bradykinin causesvascular smooth muscle relaxation by stimulating the endothelium to release prostacyclin and nitric oxide. Blood flow to the brain, heart, viscera, skeletal muscle, and glands is increased. In nonvascular smooth muscle, bradykinin will produce a contractile response.

Other actions of kinins include activation of clotting factors simultaneously with the production of brady-kinin. In the kidney, bradykinin production results in an increase in renal papillary blood flow, with a secondary inhibition of sodium reabsorption in the distal tubule. In the peripheral nervous system, bradykinin is important for the initiation of pain signals. It is also associated with the edema, erythema, and fever of inflammation.

Bradykinin exerts its physiological effects via two receptors, the B1 and B2 receptors, with most of its physiological effects being mediated by the B2 recep-tor. The precise function of the B1 receptor is unclear; however, some of the chronic inflammatory responses to bradykinin may be mediated through actions at this receptor.

Bradykinin antagonists of the B2 receptor are cur-rently in development and may find utility in the treat-ment of pain associated with burns and such chronic in-flammatory disorders as arthritis, asthma, and chronic pain.

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