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• W2125001970 abstract "Leptin has nitric oxide (NO)-dependent vasodilator actions, but hyperleptinemia is an independent risk factor for cardiovascular disease. The objective of the study was to investigate whether, in the human circulation, properties of leptin to release NO are opposed by stimulation of vasculotoxic substances, such as endothelin (ET)-1, and whether this mechanism might contribute to vascular damage in hyperleptinemic states like obesity. Forearm blood flow responses (plethysmography) to ETA receptor antagonism (BQ-123, 10 nmol/min) and NO synthase inhibition [NG-monomethyl L-arginine (L-NMMA), 4 μmol/min] were assessed before and after intraarterial administration of leptin (2 μg/min) in lean controls (n = 8) and patients with obesity-related metabolic syndrome (MetS; n = 8). Baseline plasma leptin was higher in patients than in controls (P < .001). Before infusion of leptin, the vasodilator response to BQ-123 was greater in patients than in controls (P < .001), whereas infusion of L-NMMA induced higher vasoconstriction in controls than in patients (P = .04). In lean subjects, hyperleptinemia resulted in increased vasodilator response to ETA receptor antagonism (P < .001 vs before) and enhanced vasoconstrictor effect of L-NMMA during ETA receptor blockade (P = .015 vs before). In patients with the MetS, by contrast, vascular responses to both BQ-123 and L-NMMA were not modified by exogenous leptin (both P > .05 vs before). These findings indicate that, under physiological conditions, leptin stimulates both ET-1 and NO activity in the human circulation. This effect is absent in hyperleptinemic patients with the MetS who are unresponsive to additional leptin. In these patients, therefore, hyperleptinemia may be a biomarker of vascular dysfunction, rather than a mediator of vascular damage." @default.
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• W2125001970 date "2013-03-01" @default.
• W2125001970 modified "2023-10-01" @default.
• W2125001970 title "Leptin Stimulates Both Endothelin-1 and Nitric Oxide Activity in Lean Subjects But Not in Patients With Obesity-Related Metabolic Syndrome" @default.
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• W2125001970 doi "https://doi.org/10.1210/jc.2012-3424" @default.
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