Salt-induced renal injury in spontaneously hypertensive rats: effects of nebivolol

Abstract

Background: we investigated renal effects of nebivolol, a selective β(1)-receptor blocker with additional antioxidative ability, in spontaneously hypertensive rats (SHR) where increased salt intake induces oxidative stress and worsens renal function as a result of further activation of the renin-angiotensin and sympathetic nervous systems.

Methods: male SHR were given an 8% salt diet (HS; n = 22) for 5 weeks; their age-matched controls (n = 9) received standard chow. Nebivolol was given at a dose of 10 mg/kg/day for 5 weeks in 11 HS rats.

Results: HS increased blood pressure, plasma renin concentration, urinary protein excretion, and renal nitroxidative stress while decreasing renal blood flow and angiotensin 1-7 receptor (mas) protein expression. There was no change in angiotensin II type 1 receptor expression among the experimental groups. Nebivolol did not alter the salt-induced increase in blood pressure but reduced urinary protein excretion, plasma renin concentration, and nitroxidative stress. Nebivolol also increased neuronal NOS expression while preventing the salt-induced decrease in renal blood flow and mas protein expression.

Conclusion: nebivolol prevented salt-induced kidney injury and associated proteinuria in SHR through a blood pressure-independent mechanism. Its protective effects may be related to reduction in oxidative stress, increases in neuronal NOS and restoration of angiotensin II type 1/mas receptor balance.

2010 S. Karger AG, Basel.

Figures

Fig. 1

Effects of high salt diet and nebivolol on time course of systolic tail-cuff blood pressure in SHR. * p

Fig. 2

Effects of high salt diet and nebivolol treatment on renal function. * p # p < 0.05 vs. untreated salt-loaded group.

Fig. 3

Serum and renal cortical NOx, eNOS and nNOS in the control and untreated and nebivolol-treated SHR fed high salt diet. * p # p < 0.05 vs. untreated salt-loaded group.

Fig. 4

Effects of nebivolol on 3-nitrotyrosine staining in glomeruli and proximal tubule of salt-loaded SHR. * p # p < 0.05 vs. untreated salt-loaded group.

Fig. 5

Renal intertubular fibrosis in SHR fed high salt diet and effects of nebivolol treatment. * p # p < 0.05 vs. untreated salt-loaded group.

Fig. 6

PRC and renal AT1 and mas receptor protein expression in control, salt-loaded, and nebivolol-treated SHR. AT1 = AT1 receptor; mas = mas receptor. * p < 0.05 vs. control; # p < 0.05 vs. untreated salt-loaded group.