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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Enfermedad vascular hipertensiva > DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista >

The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism
Autor(es) : Rodriguez, A. (Amaia)
Fortuño, A. (Ana)
Gomez-Ambrosi, J. (Javier)
Zalba, G. (Guillermo)
Diez, J. (Javier)
Frühbeck, G. (Gema)
Palabras clave : Angiotensin II
Vasoconstriction
Fecha incorporación: 2007
Editorial : Endocrine Society
Versión del editor: http://endo.endojournals.org/content/148/1/324
ISSN: 1945-7170
Cita: Rodriguez A, Fortuño A, Gomez-Ambrosi J, Zalba G, Diez J, Fruhbeck G. The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism. Endocrinology 2007 Jan;148(1):324-331.
Resumen
Leptin inhibits the contractile response induced by angiotensin (Ang) II in vascular smooth muscle cells (VSMCs) of the aorta. We studied in vitro and ex vivo the role of nitric oxide (NO) in the effect of leptin on the Ang II-induced vasoconstriction of the aorta of 10-wk-old Wistar rats. NO and nitric oxide synthase (NOS) activity were assessed by the Griess and (3)H-arginine/citrulline conversion assays, respectively. Stimulation of inducible NOS (iNOS) as well as Janus kinases/signal transducers and activators of transcription (JAK/STAT) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were determined by Western blot. The contractile responses to Ang II were evaluated in endothelium-denuded aortic rings using the organ bath system. Changes in intracellular Ca(2+) were measured in VSMCs using fura-2 fluorescence. Leptin significantly (P < or = 0.01) stimulated NO release and NOS activity in VSMCs. Leptin's effect on NO was abolished by the NOS inhibitor, N(G)-monomethyl l-arginine, or the iNOS selective inhibitor L-N(6)-(1-iminoethyl)-lysine. Accordingly, leptin increased iNOS protein expression, with a comparable time course with that of NO production and NOS activity. Leptin also significantly increased STAT3 (P < or = 0.01) and Akt (P < or = 0.001) phosphorylation. Moreover, either the JAK2 inhibitor, AG490, or the PI3K inhibitor, wortmannin, significantly (P < or = 0.05) abrogated the leptin-induced increase in iNOS protein. Finally, both N(G)-monomethyl L-arginine and L-N(6)-(1-iminoethyl)-lysine inhibitors completely blunted (P < or = 0.001) the leptin-mediated inhibition of the Ang II-induced VSMC activation and vasoconstriction. These findings suggest that the endothelium-independent depressor action of leptin is mediated by an increase of NO bioavailability in VSMCs. This process requires the up-regulation of iNOS through mechanisms involving JAK2/STAT3 and PI3K/Akt pathways.
Enlace permanente: http://hdl.handle.net/10171/18574
Aparece en las colecciones: DA - Medicina - Endocrinología - Artículos de revista
DA - CUN - Endocrinología y Nutrición - Artículos de revista
DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista
DA - CIFA - Laboratorio de investigación metabólica - Artículos de Revista
DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista

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Fichero:  2007 Rodríguez et al. Endocrinology 2007.pdf
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