title: Des-aspartate-angiotensin I, a novel angiotensin AT(1) receptor drug.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore. Electronic address: phcsimmk@nus.edu.sg.
authors.forename: Meng-Kwoon
authors.initials: MK
authors.lastname: Sim
mesh_terms: D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; C529402:des-aspartate-angiotensin I; D000803:Angiotensin I
keywords: Angiotensin AT(1) receptor; Des-aspartate-angiotensin I; Inflammation; Novel angiotensin receptor agonist