Hindawi Publishing Corporation Mediators of Inflammation Volume 2010, Article ID 105489, 10 pages doi:10.1155/2010/105489 Research Article Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms Amaia Rodr´ ıguez, 1, 2 Javier G ´ omez-Ambrosi, 1, 2 Victoria Catal ´ an, 1, 2 Ana Fortu˜ no, 3 and Gema Fr ¨ uhbeck 1, 2, 4 1 Metabolic Research Laboratory, University of Navarra, 31008 Pamplona, Spain 2 CIBER Fisiopatolog´ ıa de la Obesidad y Nutrici´ on, Instituto de Salud Carlos III, Spain 3 Division of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain 4 Department of Endocrinology, Cl´ ınica Universidad de Navarra, 31008 Pamplona, Spain Correspondence should be addressed to Amaia Rodr´ ıguez, arodmur@unav.es Received 4 January 2010; Revised 31 March 2010; Accepted 31 March 2010 Academic Editor: Oreste Gualillo Copyright © 2010 Amaia Rodr´ ıguez 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 3 H-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. 1. Introduction Hypertension is associated with structural changes in blood vessels known as “vascular remodelling” that include an altered proliferation, hypertrophy, migration, and apoptosis of vascular smooth muscle cells (VSMCs), together with an increased extracellular matrix abundance [1]. Angiotensin (Ang II) constitutes one of the main factors involved in vascular remodelling during the onset of hypertension [1]. Angiotensin II exerts pleiotropic actions on the vasculature, such as vasoconstriction, VSMC migration, proliferation and hypertrophy, increased extracellular matrix formation, and activation of NAD(P)H oxidases [1, 2]. Through these actions Ang II promotes vascular inflammation as well as endothelial dysfunction and structural remodelling. Leptin, the obesity gene (ob) product, participates in the control of body weight by regulating food intake and energy expenditure [3, 4]. In addition to the maintenance of energy homeostasis, leptin induces a balanced effect on the control of blood pressure (BP) with a pressor response attributable to sympathetic activation via the central nervous system and a depressor response due to a direct effect of leptin on periph- eral tissues [5]. Leptin increases the vasomotor sympathetic activity through the activation of leptin receptors (OB-R) in the ventromedial and dorsomedial hypothalamic regions [6]. On the other hand, leptin exerts a direct vasodilation