Basic and clinical aspects of bradykinin receptor antagonists

Bradykinin and related kinins may act on two types of receptors designated as B1 and B2. It seems that the B2 receptors are most commonly found in various vascular and non-vascular smooth muscles, whereas B1 receptors are formed in vitro during trauma, and injury, and are found in bone tissues. These bradykinin (BK) receptors are involved in the regulation of various physiological and pathological processes. The mode of kinin actions are based upon the interactions between the kinin and their specific receptors, which can lead to activation of several second-messenger systems. Recently, numerous BK receptor antagonists have been synthesized with prime aim to treat diseases caused by excessive kinin production. These diseases are rheumatoid arthritis (RA), inflammatory diseases of the bowel, asthma, rhinitis and sore throat, allergic reactions, pain, inflammatory skin disorders, endotoxic and anaphylactic shock and coronary heart diseases. On the other hand, BK receptor antagonists could be contraindicated in hypertension, since these drugs may antagonize the antihypertensive therapy and/ or may trigger the hypertensive crisis. It is worth suggesting that the BK receptor agonists might be useful antihypertensive drugs.