Leptin induces direct vasodilation through distinct endothelial mechanisms

Abstract

In this study, we reveal that leptin evokes an acute hypotensive effect in 6-hydroxydopamine sympathectomized rats (response to maximal leptin dose, mean blood pressure: from 92 ± 4 to 78 ± 2 mmHg, P < 0.01). This hemodynamic effect is related to a direct action of the hormone on vascular tone, since in aortic and mesenteric rings increasing doses of leptin evoke a dose-dependent vasorelaxation (aorta: from 3 ± 1 to 36 ± 3, n = 15; mesenteric: from 6 ± 1 to 30 ± 5, n = 10), which is impaired by endothelial denudation. In particular, leptin-evoked vasorelaxation is impaired by nitric oxide synthase inhibition in aorta (Δ% of maximal response: from 36 ± 3 to 3 ± 1, P < 0.01) and by endothelium-derived hyperpolarizing factor (EDHF) inhibition in mesenteric arteries (Δ% of maximal response: from 30 ± 5 to 7 ± 2, P < 0.01), suggesting that vasorelaxation evoked by leptin is heterogeneous and related to the vascular bed. Finally, the inhibition of nitric oxide synthase by N(G)-nitro-L-arginine-methyl ester does not modify blood pressure response to leptin, suggesting a predominant role of the EDHF mechanism in the hypotensive effect of leptin.