Leptin acts in the central nervous system to produce dose-dependent changes in arterial pressure

Systemic leptin increases energy expenditure through sympathetic mechanisms , decreases appetite, and increases arterial pressure. We tested the hypoth esis that the presser action of leptin is mediated by the central nervous s ystem. The interaction of dietary salt with leptin was also studied. Leptin was infused for 2 to 4 weeks into the third cerebral ventricle of Sprague- Dawley rats. Arterial pressure was measured by radiotelemetry. To control f or the effects of leptin on body weight, vehicle-treated rats were pair-fed to the leptin group. Intracerebroventricular infusion of leptin at 200 ng/ h in salt-depleted rats caused a reduction in food intake, weight loss, tac hycardia, and decreased arterial pressure. Leptin at 1000 ng/h caused furth er reduction in food intake, weight loss, and tachycardia and prevented the hypotensive effect of weight loss observed in pair-fed, vehicle-treated an imals. Intracerebroventricular leptin at 1000 ng/h in high-salt-fed rats al so caused a sustained presser response (+3+/-1 mm Hg), but high-salt intake did not potentiate the presser effect of leptin. Intracerebroventricular l eptin potentiated the presser effect of air-jet stress. Intravenous adminis tration of the same dose of leptin (1000 ng/h) did not change weight or art erial pressure, suggesting a direct central nervous system action. In contr ast, a high dose of intravenous leptin (18 000 ng/h) caused weight loss and prevented the depressor effect of weight loss. In conclusion, this study d emonstrates that high-dose leptin increases arterial pressure and heart rat e through central neural mechanisms but leptin does not enhance salt sensit ivity of arterial pressure. Leptin appears to oppose the depressor effect o f weight loss.