Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload.

The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague-Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg(-1) in bolus) (Na-Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min(-1) kg(-1)) (Na-Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FE(Na)) were measured. Ang II, NF-kappaB, hypoxia inducible factor-1 alpha (HIF-1 alpha), transforming growth factor beta1 (TGF-beta1), smooth muscle actin (alpha-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-kappaB, and TGF-beta1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1 alpha immunostaining, lower eNOS expression, and unmodified alpha-SMA. Losartan and tempol increased FE(Na) in sodium overload group. Although losartan reduced Ang II and NF-kappaB staining and increased eNOS expression, it did not restore HIF-1 alpha expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1 alpha expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1 alpha and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1 alpha expression and down-regulating TGF-beta1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects.

Rosón MI ，Della Penna SL ，Cao G ，Gorzalczany S ，Pandolfo M ，Toblli JE ，Fernández BE ... -  《-》

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》

Salt-induced downregulation of renal aquaporins is prevented by losartan.

The purpose of this study was to investigate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the renal tubule of rats fed with a high-salt diet and its modulation by the AT1 receptor blocker losartan. The experiments were performed in four groups of rats fed for 3 weeks with the following diets: regular rat chow (NS); high-salt (8% NaCl) chow (HS), NS plus losartan (NS-L) and HS plus losartan (HS-L). Losartan (40 mg x kg(-1)) was administered in the drinking water. Systolic blood pressure (SBP) and renal function were evaluated. The intrarenal levels of angiotensin II (Ang II), TGF-β(1), α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), AQP-1 and AQP-2 were determined by immunohistochemistry. AQP-1 and AQP-2 protein levels were measured by western blot analysis. A high-sodium diet downregulated AQP-1 and AQP-2 expression levels in the proximal tubule and collecting duct, respectively. The high-sodium diet also induced Ang II, TGF-β(1) and α-SMA overexpression and decreased eNOS expression in the renal cortex and medulla. Losartan increased the diuresis and natriuresis, favoring urinary sodium concentration. Additionally, losartan prevented the profibrogenic response, decreasing Ang II, TGF-β(1) and α-SMA levels and normalizing AQP-2 expression in the HS-L group. AQP-1 expression was upregulated by losartan in both the NS-L and HS-L groups. These results show that increased intrarenal Ang II in rats fed with a high-salt diet downregulates renal AQP-1 and AQP-2 expressions. In addition, although losartan increased diuresis and natriuresis, it prevented the downregulation of aquaporins, favoring urinary sodium concentration.

Della Penna SL ，Cao G ，Fellet A ，Balaszczuk AM ，Zotta E ，Cerrudo C ，Pandolfo M ，Toblli JE ，Fernández BE ，Rosón MI ... -  《-》

Adverse effects of tempol on hidrosaline balance in rats with acute sodium overload.

Kouyoumdzian NM ，Mikusic NR ，Cao G ，Choi MR ，Penna SD ，Fernández BE ，Toblli JE ，Rosón MI ... -  《-》

Involvement of oxidative stress in the profibrotic action of aldosterone. Interaction wtih the renin-angiotension system.

Iglarz M ，Touyz RM ，Viel EC ，Amiri F ，Schiffrin EL ... -  《AMERICAN JOURNAL OF HYPERTENSION》