Angiotensin II increases intrarenal transforming growth factor-beta1 in rats submitted to sodium overload independently of blood pressure.

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-beta1 (TGF-beta1) observed in rats submitted to sodium overload. Sprague-Dawley-rats were infused for 2 h with 0.1 and 5 microg 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-beta1, alpha-smooth-muscle-actin (alpha-SMA) and nuclear factor-kappaB (NF-kappaB) 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-beta1 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-beta 1 immunostaining compared to the Na 0.5 group. Peritubular positive staining for alpha-SMA was present in groups receiving Ang alone or Ang-Na, in a sodium concentration-dependent manner. In cortical-tubules, NF-kappaB 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-beta1, alpha-SMA and NF-kappaB immunostanding in glomeruli, medullary tubules and renal vessels. In conclusion, the interaction of Ang II with acute-sodium overload exacerbated intrarenal TGF-beta1, alpha-SMA and NF-kappaB expression, independently from changes in blood pressure levels, in normal rats.