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Mediators of Inflammation
Volume 2010, Article ID 105489, 10 pages
Research Article

Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms

1Metabolic Research Laboratory, University of Navarra, 31008 Pamplona, Spain
2CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
3Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain
4Department of Endocrinology, Clínica Universidad de Navarra, 31008 Pamplona, Spain

Received 4 January 2010; Revised 31 March 2010; Accepted 31 March 2010

Academic Editor: Oreste Gualillo

Copyright © 2010 Amaia Rodríguez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO). Methods. NO and NO synthase (NOS) activity were assessed by the Griess and 3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS) and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods. Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated. Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.