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

作者：Sim Meng Kwoon^*

来源：European Journal of Pharmacology, 2015, 760: 36-41.

DOI：10.1016/j.ejphar.2015.04.004

• Des-aspartate-angiotensin I
• Angiotensin AT(1) receptor
• Novel angiotensin receptor agonist
• Inflammation

The review describes DAA-I (des-aspartate-angiotensin-l) as a prototype of a novel class of drugs that acts as agonists on the angiotensin AT, 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 Ill 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 AT(1) 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.

• 出版日期2015-8-5