Angiotensin II Increases Intrarenal Transforming Growth Factor-β1 in Rats Submitted to Sodium Overload Independently of Blood Pressure

Abstract

Angiotensin II (Ang II) promotes sodium-retention, cell growth and fibrosis in addition to its classical effects on blood pressure and fluid homeostasis. In this study we examined whether low and non-hypertensive doses of exogenous Ang II could enhance the intrarenal expression of transforming growth factor-β1 (TGF-β1) observed in rats submitted to sodium overload. Sprague-Dawley-rats were infused for 2 h with 0.1 and 5 μg kg⁻¹ h⁻¹ Ang II (Ang 0.1 and Ang 5, respectively) together with saline solution at four different concentrations (isotonic and Na 0.5 mol L⁻¹, Na 1.0 mol L⁻¹ and Na 1.5 mol L⁻¹). Renal function and mean arterial blood pressure (BP) were measured. The renal distributions of TGF-β1, α-smooth-muscle-actin (α-SMA) and nuclear factor-κB (NF-κB) were evaluated by immunohistochemistry. While the Ang 0.1 groups were normotensive, the Ang 5 groups developed arterial hypertension progressively, and the highest blood pressure values were observed when rats were simultaneously infused with Na 1.5 mol L⁻¹. Glomerular function was not altered in any group. In cortical tubules, all groups infused with Ang II (0.1 and 5) and hypertonic saline solution (HSS) showed an increase in TGF-β1 immunostaining compared to those infused with HSS alone. In medullary tubules, only the Ang 5–Na 0.5 group showed a significant increase in TGF-β 1 immunostaining compared to the Na 0.5 group. Peritubular positive staining for α-SMA was present in groups receiving Ang alone or Ang-Na, in a sodium concentration–dependent manner. In cortical-tubules, NF-κB immunostaining was significantly increased in the Ang groups in comparison with the control and in Ang–Na 0.5 and Ang–Na 1.0 groups in comparison with the Na 0.5 mol L⁻¹ and Na 1.5 mol L⁻¹ groups, respectively, except in the case of the Ang 0.1–Na 1.5 mol L⁻¹ and Ang 5–Na 1.5 mol L⁻¹ groups. Moreover, Ang II and sodium overload induced additional changes in TGF-β1, α-SMA and NF-κB immunostanding in glomeruli, medullary tubules and renal vessels. In conclusion, the interaction of Ang II with acute-sodium overload exacerbated intrarenal TGF-β1, α-SMA and NF-κB expression, independently from changes in blood pressure levels, in normal rats.