Systemic infusion of angiotensin II into normal rats activates nuclear factor-kappa B and AP-1 in the kidney - Role of AT(1) and AT(2) receptors

Recent studies have pointed out the implication of angiotensin II (Ang II) in various pathological settings. However, the molecular mechanisms and the AngII receptor (AT) subtypes involved are not fully identified. We investi gated whether AngII elicited the in vivo activation of nuclear transcriptio n factors that play important roles in the pathogenesis of renal and vascul ar injury. Systemic infusion of Ang II into normal rats increased renal nuc lear factor (NF)-kappaB and AP-1 binding activity that was associated with inflammatory cell infiltration and tubular damage. Interestingly, infiltrat ing cells presented activated NF-kappaB complexes, suggesting the involveme nt of AngII in inflammatory cell activation. When rats were treated with AT (1) or AT(2) receptor antagonists different responses were observed. The AT (1) antagonist diminished NF-kappaB activity in glomerular and tubular cell s and abolished AP-1 in renal cells, improved tubular damage and normalized the arterial blood pressure. The AT(2) antagonist diminished mononuclear c ell infiltration and NF-kappaB activity in glomerular and inflammatory cell s, without any effect on AP-1 and blood pressure. These data suggest that A T(1) mainly mediates tubular injury via AP-1/NF-kappaB, whereas AT(2) recep tor participates in the inflammatory cell infiltration in the kidney by NF- kappaB, Our results provide novel information on AngII receptor signaling a nd support the recent view of Ang II as a proinflammatory modulator.