Short-term physiological hyperleptinemia decreases arterial blood pressure

We examined the possibility that chronic, low-dose peripheral leptin infusion would inhibit food intake but not increase blood pressure. Male Fisher Brown Norway (FBNF1) and Sprague–Dawley (SD) rats were instrumented for cardiovascular telemetry, housed in metabolic chambers, and given leptin (LEP: 600 µg/kg/day) or vehicle (SAL: 10 µl/h) via a subcutaneous osmotic pump for seven days. Leptin infusion increased plasma leptin levels to about 40 ng/ml, decreased food intake by 25–35% and stimulated lipolysis in both strains of rats. Leptin infusion for one week decreased mean arterial pressure from baseline. The reduction developed slowly, was generally about 3 to 7 mm Hg, and observed in both strains. The peripheral, hypotensive effect of chronic leptin in FBNF1 rats was prevented by blockade of nitric oxide production with L-NAME treatment. These results indicate that peripheral leptin treatment, at a level which inhibits food intake and induces lipolysis, produces nitric oxide-dependent decreases in blood pressure.