Des-aspartate-angiotensin I, a novel angiotensin AT(1) receptor drug.

The review describes DAA-I (des-aspartate-angiotensin-I) as a prototype of a novel class of drugs that acts as agonists on the angiotensin AT1 receptor or ARAs (angiotensin receptor agonists). DAA-I is a component of the renin angiotensin system. Earlier studies showed that it was rapidly metabolized to angiotensin III. However, when administered at doses below the Km of enzymes, DAA-I produces specific actions that antagonize the deleterious actions of angiotensin II. DAA-I exerts protective actions in animal models of eight human pathologies in which angiotensin II is implicated. The pathologies include cardiac hypertrophy, neointima growth and cardiovascular hypertrophy, myocardial-ischemia reperfusion injury, hyperglycemia and insulin resistance, chemical induced inflammation, and exercise-induced skeletal muscle inflammation. Binding of DAA-I to the angiotensin AT1 receptors releases prostaglandins, which could either function as autocrines/paracrines or second messengers and attenuate the deleterious actions of angiotensin II. It is possible that in in vivo DAA-I functions as a physiological antagonist to angiotensin II, and exogenous DAA-I is a novel class of angiotensin receptor drug that could rival the angiotensin receptor blockers.