Leptin induces direct vasodilation through distinct endothelial mechanisms.
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.
Lembo
G
G
Instituto di Ricovero e Cura a Carattere Scientifico, NEUROMED, Pozzilli, Italy. glembo@connect.it
Vecchione
C
C
Fratta
L
L
Marino
G
G
Trimarco
V
V
d'Amati
G
G
Trimarco
B
B
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020738:Leptin / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D014664:Vasodilation; D014666:Vasomotor System / Q000187:drug effects
D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins