Targeting kinin receptors for the treatment of tissue ischaemia

Kinins, the biological end-products of the kallikrein-kininogen system, inf luence many aspects of the cellular function. Interest in this peptidergic system has been renewed recently by the discovery that kinins exert cardiov ascular protective effects and promote post-ischaemic recovery by stimulati ng vascular growth. Pharmacological and genetic studies indicate that induc tion of kallikrein and kinin receptors by ischaemia is functionally relevan t in the natural host response that permits perfusion recovery and tissue h ealing. Furthermore, potentiation of the generation of kinins by continuous supply of tissue kallikrein promotes reparative angiogenesis through stimu lation of the release of nitric oxide and prostaglandins. Strategies that a ctivate kinin receptors might be applicable to the treatment of occlusive v ascular disease, whereas kinin receptor antagonists could represent therape utic reagents against pathological angiogenesis in cancer and chronic infla mmatory conditions.