Does leptin stimulate nitric oxide to oppose the effects of sympathetic activation?

Leptin decreases appetite and increases sympathetic nerve activity and arte rial pressure. Recent reports suggest that leptin may also have peripheral vasodilator actions that would tend to reduce arterial pressure. We tested the hypothesis that the direct vascular actions of leptin oppose sympatheti cally mediated vasoconstriction. We evaluated the effects of intravenous le ptin (1 mg/kg over 3 hours) on arterial pressure and mesenteric, hindlimb, and renal blood flows in conscious rats. We then tested whether blockade of nitric oxide or the sympathetic nervous system would unmask a pressor or d epressor effect of leptin, consistent with direct vascular actions. Acute i ntravenous administration of leptin alone did not change arterial pressure or regional blood flows. This was despite a significant increase in lumbar sympathetic nerve activity. Administration of the nitric oxide synthase inh ibitor NG-nitro-L-arginine methyl ester significantly increased arterial pr essure and caused vasoconstriction. However, leptin did not have any signif icant effect on hemodynamics in the presence of N-G-nitro-L-arginine methyl ester despite continued sympathoactivation. a-Adrenoceptor blockade with p razosin alone or combined with yohimbine significantly decreased arterial p ressure and caused vasodilation. Again, leptin did not have any effect on a rterial pressure or regional blood flow in the presence of sympathetic bloc kade. These data demonstrate that leptin does not have vasodilator actions in vivo at concentrations that are sufficient to increase sympathetic nerve activity. The absence of a pressor effect of leptin-induced sympathetic ac tivation may merely reflect the brief duration of leptin administration. Th ese data support the concept that the chronic hemodynamic actions of leptin are likely to be related to sympathetic activation.