Antioxidant treatment normalizes nitric oxide production, renal sodium handling and blood pressure in experimental hyperleptinemia.
Recent studies suggest that adipose tissue hormone, leptin, is involved in the pathogenesis of arterial hypertension. However, the mechanism of hypertensive effect of leptin is incompletely understood. We investigated whether antioxidant treatment could prevent leptin-induced hypertension. Hyperleptinemia was induced in male Wistar rats by administration of exogenous leptin (0.25 mg/kg twice daily s.c. for 7 days) and separate groups were simultaneously treated with superoxide scavenger, tempol, or NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water). After 7 days, systolic blood pressure was 20.6% higher in leptin-treated than in control animals. Both tempol and apocynin prevented leptin-induced increase in blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes increased in leptin-treated rats by 66.9% and 67.7%, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals (MDA+4-HNE), was 60.3% higher in the renal cortex and 48.1% higher in the renal medulla of leptin-treated animals. Aconitase activity decreased in these regions of the kidney following leptin administration by 44.8% and 45.1%, respectively. Leptin increased nitrotyrosine concentration in plasma and renal tissue. Urinary excretion of nitric oxide metabolites (NO(x)) was 57.4% lower and cyclic GMP excretion was 32.0% lower in leptin-treated than in control group. Leptin decreased absolute and fractional sodium excretion by 44.5% and 44.7%, respectively. Co-treatment with either tempol or apocynin normalized 8-isoprostanes, MDA+4-HNE, aconitase activity, nitrotyrosine, as well as urinary excretion of NO(x), cGMP and sodium in rats receiving leptin. These results indicate that oxidative stress-induced NO deficiency is involved in the pathogenesis of leptin-induced hypertension.
Beltowski
Jerzy
J
Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland. jerzybel@hotmail.com
Wójcicka
Grazyna
G
Jamroz-Wiśniewska
Anna
A
Borkowska
Ewelina
E
Marciniak
Andrzej
A
D000098:Acetophenones / Q000494:pharmacology; D000154:Aconitate Hydratase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003401:Creatine / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D028421:Isoprostanes / Q000097:blood / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000097:blood / Q000652:urine; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013113:Spin Labels; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D000098:Acetophenones; D000447:Aldehydes; D000975:Antioxidants; D003497:Cyclic N-Oxides; D028421:Isoprostanes; D020738:Leptin; D026361:Reactive Nitrogen Species; D013113:Spin Labels; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D012964:Sodium; C056165:acetovanillone; D000154:Aconitate Hydratase; D006152:Cyclic GMP; C027576:4-hydroxy-2-nonenal; D003401:Creatine; C001803:tempol