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.

Research Methods And Procedures: 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.

Discussion: 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.