Stimulatory effect of leptin on nitric oxide production is impaired in dietary-induced obesity.
OBJECTIVE
We investigated the effect of leptin on nitric oxide production in lean and rats made obese by a high-calorie diet.


METHODS
The animals were placed in metabolic cages, and urine was collected in 2-hour periods after leptin (1 mg/kg intraperintoneally) or vehicle administration. Blood was obtained 0.5, 1, 2, 4, or 6 hours after injection.


RESULTS
Leptin had no effect on systolic blood pressure in either lean or obese animals. Plasma concentration of NO metabolites (nitrites + nitrates, NOx) increased in lean rats by 31.5%, 58.0%, and 27.9% at 1, 2, and 4 hours after leptin injection, respectively. In the obese group, plasma NOx increased only at 2 hours (+36.5%). Leptin increased urinary NOx excretion by 31.8% in the first 2-hour period after injection in lean but not in obese rats. In lean animals, leptin elevated plasma cyclic 3',5'-guanosine monophosphate (cGMP) at 1, 2, and 4 hours by 35.3%, 96.3%, and 57.3%, respectively. In the obese group, plasma cGMP was higher only at 2 and 4 hours (+44.6% and +32.1%, respectively). Urinary excretion of cGMP increased in lean animals by 67.1% in the first period and by 50.4% in the second period. In the obese group, leptin induced a 53.9% increase in urinary cGMP excretion only in the first 2-hour period.


CONCLUSIONS
The stimulatory effect of leptin on NO production is impaired in dietary-induced obesity; however, leptin does not increase blood pressure in obese animals, suggesting that other NO-independent depressor mechanisms are stimulated.
Bełtowski
Jerzy
J
Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland. jerzybel@hotmail.com
Wójcicka
Grazyna
G
Jamroz
Anna
A
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism / Q000652:urine; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D020738:Leptin; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D006152:Cyclic GMP