Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat

Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant-induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT₁ pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100 µL of an emulsion of dissected Mycobacterium tuberculosis (50 mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1 mg/kg). After 60 days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF-β) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT₁ ) and 2 (AT₂ ) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF-β, caspase-3, iNOS and AT₁ /AT₂ receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-β and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT₁  stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF-β and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.