Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance

Abstract

Aims: We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease. Methods and results: In 131 patients (age 65.7±0.7 years mean±SEM), ex vivo vascular reactivity to leptin (10-13-10-7 M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5±1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4±3.4 vs.17.8±3.3%, P=0.9) or endothelial denudation (17.4±4.4 vs. 22.5±3.0%, P=0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08±4.1%, P<0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r=0.25, P<0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature. Conclusion: Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions. © The European Society of Cardiology 2006. All rights reserved.