Angiotensin II type 2 receptor agonists--where should they be applied?

It is now widely accepted that the renin-angiotensin system (RAS) not only contributes to pathological mechanisms involved, e.g. in hypertension or hypertensive and diabetic end-organ damage, but also harbors a "protective arm" represented mainly by two receptors, the AT2 (angiotensin type 2) receptor and the Mas receptor, both mediating tissue-protective and pro-regenerative actions. Several compounds are currently in preclinical and clinical development, which aim at targeting the "protective RAS" by agonism on the AT2 or the Mas receptor. In a recent issue of Expert Opinion on Investigational Drugs Koen Verdonk and co-authors review the physiology and patho-physiology of the AT2 receptor and discuss potential future clinical indications and putative adverse effects of AT2 receptor agonists. This article comments the review by Verdonk et al., suggests some additional possible indications, and particularly re-reviews whether there is preclinical in vivo evidence for adverse effects of AT2 receptor agonists.