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-ß) 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-ß, caspase-3, iNOS and AT1 /AT2 receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-ß 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-ß and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.

Effects of adjuvant-induced arthritis on the ventral prostate of rats treated with angiotensin AT1 receptor blocker.

AIMS: To analyze the prostatic compartments, extracellular matrix, microvascularization, transforming growth factor-beta (TGF-ß) and angiotensin II receptors type 1 (AT1) levels, and histopathology of the ventral prostate in a rat model for rheumatoid arthritis, and to evaluate the effect of angiotensin II AT1 receptor blocker (ARB) in the disease. MAIN METHODS: Fifteen male rats (90 days old) were divided into three groups (n = 5/group): control, adjuvant-induced arthritis without (AIA) or with AT1 receptor blocker (AIA + ARB). Animals were euthanized 60 days after immunization. The ventral prostate was collected, weighed, and processed for histological and immunohistochemical analysis. KEY FINDINGS: Our results show that AIA increases production of the prostatic epithelium and extracellular matrix, accompanied by a reduction in the number of tissue capillaries. ARB treatment promotes decreased production of extracellular matrix and increased TGF-ß and AT1 receptor immunostaining. SIGNIFICANCE: AIA may activate specific mechanisms that modify the prostatic environment; the use of ARB attenuates some altered prostate parameters in a rat model for arthritis.