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 (delta% of maximal response: from 36 +/- 3 to 3 +/- 1, P < 0.01) and by endothelium-derived hyperpolarizing factor (EDHF) inhibition in mesenteric arteries (delta% 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 NG-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.
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Abstract|
February 01 2000
Leptin induces direct vasodilation through distinct endothelial mechanisms.
G Lembo;
G Lembo
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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C Vecchione;
C Vecchione
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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L Fratta;
L Fratta
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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G Marino;
G Marino
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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V Trimarco;
V Trimarco
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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G d'Amati;
G d'Amati
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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B Trimarco
B Trimarco
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
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Citation
G Lembo, C Vecchione, L Fratta, G Marino, V Trimarco, G d'Amati, B Trimarco; Leptin induces direct vasodilation through distinct endothelial mechanisms.. Diabetes 1 February 2000; 49 (2): 293–297. https://doi.org/10.2337/diabetes.49.2.293
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