Vascular protective effects of Angiotensin Receptor Blockers: Beyond Blood pressure.

Angiotensin-II (Ang-II) activates two major types of receptors, angiotensin II type one (AT1R) and type two (AT2R) receptors. While AT1R is widely expressed and mediates most inflammatory Ang-II effects, AT2R, is less expressed and has opposite effects, promoting vasodilation and anti-inflammatory effects . Physiologically, AT2R actions are usually masked by the more abundant AT1R. It has been suggested that ARBs can mediate their action through increasing angiotensin II (Ang II) availability to bind to the beneficial angiotensin type 2 receptor (AT2R), thus leading to unopposed AT2R stimulation. AT1R blockers (ARBs) represent a major class of antihypertensive medications. They are considered first line treatment for essential hypertension. Moreover, ARBs are the cornerstone treatment for other cardiovascular diseases especially in patients with diabetic and renal comorbidities. Clinical and experimental evidence have documented the beneficial actions of ARBs beyond the blood pressure lowering effect. Ischemic diseases such as stroke and proliferative retinopathy are characterized by hypoxia-driven release of angiogenic growth factors . However, revascularization of the ischemic areas is inadequate, resulting in impaired neuro-vascular function. ARBs have been shown to exhibit vascular protective and proor anti-angiogenic effects depending on the tissue/cell type and disease condition under study . Our group has demonstrated the vascular protective effects of ARBs and candesartan, in particular, in models of ischemic stroke and retinopathy. The positive impact of candesartan was mainly via enhancing the proangiogenic state and stimulation of reparative angiogenesis. This commentary aims to highlight the recently identified pathways engaged as a result of directly blocking the AT1 receptor or indirectly by possible activation of AT2 receptor, in the context of the published literature.