Cardiovascular and renal function of angiotensin II type-2 receptors

While all of the well-known cardiovascular and renal effects of angiotensin II (ANG) are attributed to the ANG type-1 (AT₁) receptor, much less is known about the function of ANG type-2 (AT₂) receptors. This review focuses on progress made in AT₂ receptor research over the past 10 years mainly enabled by the availability of AT₂ receptor-deficient mice. Two general mechanisms regarding AT₂ receptor-mediated actions emerge from recent experiments. Firstly, AT ₂ receptor stimulation inhibits growth and promotes apoptosis, an important mechanism during development and tissue remodeling. Secondly, ANG stimulates the release of nitric oxide (NO)/cGMP via AT₂ receptor activation, as described in the aorta, heart, and kidney. This effect appears to be indirectly mediated by the modulation of bradykinin release. Thus, activation of AT₂ receptors may be potentially protective and appears to oppose the effects mediated by AT₁ receptors. The question whether AT₂ receptors are activated in patients with elevated ANG levels when treated with AT₁ receptor antagonists and whether these effects are relevant awaits further clarification.