Original research article Hypotensive effects of omentin-1 related to increased adiponectin and decreased interleukin-6 in intra-thoracic pericardial adipose tissue Luigi Brunetti, Sheila Leone, Giustino Orlando, Claudio Ferrante, Lucia Recinella, Annalisa Chiavaroli, Chiara Di Nisio, Rugia Shohreh, Fabio Manippa, Adriana Ricciuti, Michele Vacca * Department of Pharmacy, ‘‘G. d’Annunzio’’ University, Chieti, Italy Introduction The adipose tissue, besides its energy storage role, is also recognized as a key endocrine organ that secretes a variety of bioactive molecules from different cell types. Omentin is a recently identified 313 amino acid adipocytokine which is secreted by visceral stromal vascular cells [1,2]. Omentin-1 is the major circulating isoform in human plasma [3]. Reduced omentin-1 levels are associated with low plasma adiponectin and high- density lipoprotein levels. In addition, omentin-1 levels are negatively correlated with leptin levels, waist circumference, body mass index, and insulin resistance [3]. On the other hand, preliminary experiments showed negative effects on leptin gene expression in several tissues, including visceral adipose tissue (VAT) and hypothalamus, after subacute omentin-1 administration [4]. The inverse correlation of omentin-1 levels with markers of obesity and the link between obesity and cardiovascular disease (CVD) suggest a possible role for omentin-1 in CVD as well. Several studies point to alterations in epicardial adipose tissue (EAT) in the pathophysiology of CVD due to close proximity to the heart and coronary vessels and production of pro-inflammatory adipokines [5–7]. Most of these molecules, such as leptin, plasminogen- activator inhibitor type 1, tumor necrosis factor-a (TNF-a) and Pharmacological Reports 66 (2014) 991–995 A R T I C L E I N F O Article history: Received 15 October 2013 Received in revised form 9 May 2014 Accepted 5 June 2014 Available online 26 June 2014 Keywords: Adiponectin Hypotension Interleukin-6 L-Citrulline Omentin-1 A B S T R A C T Background: Omentin is an adipokine expressed in visceral adipose tissue (VAT). In vitro studies demonstrated that omentin induces vasorelaxation in isolated rat mesenteric arteries, and in vivo studies showed inhibition of agonist-induced increases in blood pressure, possibly mediated by nitric oxide (NO)-dependent mechanisms. Methods: We investigated, in normotensive rats, the effects of subacute omentin-1 administration [8 mg/kg, intraperitoneally (ip), once daily for 14 days] on cardiac activity, blood pressure, plasma concentration of L-citrulline (as a marker of NO production from L-arginine), and the gene expression of adiponectin, tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) in intra-thoracic pericardial adipose tissue (PAT). Electrocardiography (ECG), heart rate (HR), mean blood pressure (MBP), pulse pressure (PP) were monitored before and after treatment with omentin-1 or vehicle. Results: With respect to baseline and vehicle, we found a significant decrease of MBP (p < 0.005) and PP (p < 0.05) after treatment with omentin-1, while ECG and HR were not modified. Omentin-1 significantly increased L-citrulline levels in plasma (p < 0.05), and the gene expression of adiponectin in PAT (p < 0.05). On the other hand, we found decreased gene expression of IL-6 (p < 0.005), while TNF- a mRNA in PAT was not affected. Conclusion: We conclude that the hypotensive effects of omentin-1 could be driven by stimulated production of NO in the vascular system, possibly related to increased adiponectin and decreased IL-6 mRNA in PAT. ß 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved. Abbreviations: BP, blood pressure; EAT, epicardial adipose tissue; ECG, electrocar- diography; CVD, cardiovascular disease; HR, heart rate; IL-6, interleukin-6; MBP, mean blood pressure; NO, nitric oxide; PAT, intra-thoracic pericardial adipose tissue; PP, pulse pressure; TNF-a, tumor necrosis factor-a; Real-time PCR, real-time reverse transcription polymerase chain reaction; HPLC, high performance liquid chromatography. * Corresponding author. E-mail address: mvacca@unich.it (M. Vacca). Contents lists available at ScienceDirect Pharmacological Reports jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/p h arep http://dx.doi.org/10.1016/j.pharep.2014.06.014 1734-1140/ß 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.