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


CONCLUSIONS
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.
Hypertension and Vascular Research Center, Wake Forest University, Winston-Salem, NC 27157, USA. jvaragic@wfubmc.edu
Jasmina
J
Varagic
Sarfaraz
S
Ahmad
K Bridget
KB
Brosnihan
Javad
J
Habibi
Roger D
RD
Tilmon
James R
JR
Sowers
Carlos M
CM
Ferrario
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control; D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000068577:Nebivolol; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012965:Sodium Chloride / Q000009:adverse effects*
D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000068577:Nebivolol; D000804:Angiotensin II; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D012083:Renin