Direct anti‐inflammatory effects of angiotensin‐(1–7) on microglia

Much evidence indicates that pro‐inflammatory effects of the renin–angiotensin system within the hypothalamus, including microglial activation and production of pro‐inflammatory cytokines, play a role in chronic neurogenic hypertension. Our objective here was to examine whether angiotensin‐(1–7) [Ang‐(1–7)], a protective component of the renin–angiotensin system, exerts direct actions at microglia to counteract these pro‐inflammatory effects. Mas, the Ang‐(1–7) receptor, was shown to be present on cultured hypothalamic microglia. Treatment of these cells with Ang‐(1–7) (100–1000 nM, 3–12 h) elicited significant decreases in basal levels of mRNAs for the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and tumor‐necrosis factor α (TNFα) and of the microglia‐macrophage marker CD11b, and increases in basal levels of the anti‐inflammatory cytokine interleukin‐10. Incubation of microglial cultures with (pro)renin (PRO) (10–50 nM; 6 h) elicited significant increases in mRNAs for IL‐1β, TNFα and CD11b. The effects of PRO (10 nM) on IL‐1β and TNFα mRNAs, and TNFα protein, were significantly attenuated by co‐treatment with Ang‐(1–7) (100 nM). Lastly, these actions of Ang‐(1–7) were abolished by the Mas antagonist A‐779, and were associated with reductions in NF‐κB subunit expression. Collectively, these data provide the first evidence that Ang‐(1–7) can exert direct effects at microglia to lower baseline and counteract PRO‐induced increases in pro‐inflammatory cytokines. Renin‐Angiotensin system mediated microglial activation and pro‐inflammatory cytokine production within the hypothalamus are components of the chronic neuroinflammation associated with ‘neurogenic’ hypertension. We demonstrated that angiotension‐(1–7) acting via its receptor Mas on hypothalamic microglia lessens baseline and (pro)renin‐induced increases in pro‐inflammatory cytokine production by these cells. This is the first evidence that angiotensin‐(1–7) has direct anti‐inflammatory effects via microglia. Renin‐Angiotensin system mediated microglial activation and pro‐inflammatory cytokine production within the hypothalamus are components of the chronic neuroinflammation associated with ‘neurogenic’ hypertension. We demonstrated that angiotension‐(1–7) acting via its receptor Mas on hypothalamic microglia lessens baseline and (pro)renin‐induced increases in pro‐inflammatory cytokine production by these cells. This is the first evidence that angiotensin‐(1–7) has direct anti‐inflammatory effects