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

ROSÓN MI, CAO G, DELLA PENNA S, GORZALCZANY S, PANDOLFO M, TOBLLI JE, FERNÁNDEZ BE

HYPERTENSION RESEARCH

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2008 p. 707 - 715

0916-9636

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.