Antioxidant treatment normalizes renal Na+,K+-ATPase activity in leptin-treated rats.
Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin is incompletely elucidated. Previously, we have demonstrated that chronic hyperleptinemia causes up-regulation of renal Na+,K+-ATPase and decreases urinary Na+ excretion. Herein, we investigated whether antioxidant treatment could correct these abnormalities. The study was performed on male Wistar rats. Leptin administered for 7 days (0.25 mg/kg twice daily sc) increased systolic blood pressure by 20.6%. Leptin had no effect on urine output and creatinine clearance but reduced sodium excretion by 40.1%. Na+,K+-ATPase activity in the renal cortex and medulla was higher in leptin-treated rats by 24.3% and 80.6%, respectively. In addition, hyperleptinemia was associated with an increase in plasma and urinary 8-isoprostanes and reduced urinary excretion of nitric oxide (NO) metabolites and cGMP. Co-treatment with a superoxide dismutase mimetic, tempol, or an NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water), prevented leptin-induced blood pressure elevation, normalized plasma and urinary 8-isoprostanes, urinary excretion of sodium, NO metabolites and cGMP, as well as prevented up-regulation of renal Na+,K+-ATPase activity. These data suggest that hyperleptinemia increases renal Na+,K+-ATPase activity and reduces natriuresis by inducing oxidative stress-dependent NO deficiency. Antioxidant treatment is effective in leptin-induced hypertension and should be considered in controlling blood pressure in hyperleptinemic obese individuals.
Bełtowski
Jerzy
J
Department of Pathophysiology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland. jerzybe@hotmail.com
Jamroz-Wiśniewska
Anna
A
Borkowska
Ewelina
E
Nazar
Jarosław
J
Marciniak
Andrzej
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007677:Kidney Function Tests; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000975:Antioxidants; D020738:Leptin; D009569:Nitric Oxide; D003404:Creatinine; D000254:Sodium-Potassium-Exchanging ATPase