Stimulatory Effect of Leptin on Nitric Oxide Production Is Impaired in Dietary‐Induced Obesity

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<jats:title>Abstract</jats:title><jats:p><jats:italic>Objective</jats:italic>: We investigated the effect of leptin on nitric oxide production in lean and rats made obese by a high‐calorie diet.</jats:p><jats:p><jats:italic>Research Methods and Procedures</jats:italic>: 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.</jats:p><jats:p><jats:italic>Results</jats:italic>: Leptin had no effect on systolic blood pressure in either lean or obese animals. Plasma concentration of NO metabolites (nitrites + nitrates, NO<jats:sub>x</jats:sub>) 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 NO<jats:sub>x</jats:sub> increased only at 2 hours (+36.5%). Leptin increased urinary NO<jats:sub>x</jats:sub> 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.</jats:p><jats:p><jats:italic>Discussion</jats:italic>: 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.</jats:p>

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