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 microg/kg/day) or vehicle (SAL: 10 microl/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.