Clinical and Experimental Hypertension, 32, 98–104, 2010 Copyright © Informa UK Ltd. ISSN: 1064-1963 print / 1525-6006 online DOI: 10.3109/10641960902993129 98 LCEH Effect of Losartan on Vascular Function in Fructose-Fed Rats: The Role of Perivascular Adipose Tissue Losartan on the PVAT-Associated Vascular Function Fengyang Huang 1 , Miguel Angel Rosas Lezama 2 , José Alfredo Pérez Ontiveros 1 , Guadalupe Bravo 2 , Santiago Villafaña 3 , Blanca Estela del-Rio-Navarro 4 , Enrique Hong 2 1 Department of Pharmacology and Toxicology, Hospital Infantil de México Federico Gómez, México 2 Department of Pharmacobiology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Naciónal, México 3 Sección de Posgrado, Escuela Superior de Medicina del Instituto Politécnico Nacional, México 4 Departament of Allergy, Hospital Infantil de México Federico Gómez, México ABSTRACT Recent studies have shown the effect of perivascular adipose tissue (PVAT) on the regulation of vascular func- tion; however, its role in the model of metabolic syndrome remains unclear. The aim of this study was to examine the effect of losartan on PVAT-derived vascular dysfunction in fructose-induced hypertensive rats. Rats were fed with either water, 10% fructose, or 10% fructose with 10mg/kg losartan for 8 weeks. In the isolated aorta with PVAT and endothelium, contraction induced by norepinephrine (NE) was more potent in fructose-fed rats com- pared to control rats. Losartan normalized blood pressure, insulin resistance, and NE-induced vasoconstriction in fructose-fed rats. In the aortic rings with/without endothelium and with/without PVAT, losartan could not improve the acetylcholine-induced relaxation in fructose-fed rats. The observation suggested that losartan partly improved the PVAT-associated vascular regulation in fructose-induced hypertensive rats. KEYWORDS: losartan; perivascular adipose tissue; vascular function; hypertension; fructose INTRODUCTION Perivascular adipose tissue (PVAT) is situated outside the adventitial layer and surrounds most of the systemic blood vessels. Recent studies have shown that PVAT can attenuate vessel contraction to various agonists in the aorta and mesenteric arteries of rats and human (1–3). The mechanisms for the attenuation of contrac- tion by PVAT are not fully understood, but the release of transferable relaxation factor(s) with unknown iden- tity, termed adventitium-derived relaxation factor (ADRF) or perivascular adipose tissue-derived relax- ation factor (PVRF) have been proposed (1,2,4–7). Studies demonstrated that rat and human adipose tissue possess all of the components needed for pro- duction of angiotensin II (Ang II), including angio- tensinogen, renin-like activity, angiotensin-converting enzyme (ACE), and Ang II type 1 (AT1) (8–15). Thus alterations of renin-angiotensin system (RAS) in adipose tissue have the ability to impact the systemic RAS and influence blood pressure. The evidence suggested that AT1-mediated Ang II signaling is essen- tial for the maintenance of systemic blood pressure (SBP) in the insulin-resistance state. It is generally accepted that blockade of RAS with an ACE inhibitor or AT1 receptor antagonists has been noted to improve vascular reactivity on patients with insulin-resistance (16–18), Little is known-However, about the effect of ACE inhibitor and AT1 receptor antagonists on the PVAT-associated vascular reactivity. Fructose-fed rats (FFRs) provide a model of insu- lin-resistance and hypertension (19–20). In the present study, we tested the hypothesis that the attenuated vasodilatation of perivascular adipose tissue contrib- utes to the hypertension in the experimental model of metabolic syndrome. Furthermore, we examined the effect of chronic administration of losartan, an antago- nist of AT1 receptor, on the perivascular adipose- derived vasodilatation. METHODS Animals and Experimental Design All procedures were performed according to institu- tional guidelines for animal experimentation. Male Received 20 October, 2008; revised 25 November, 2008; accepted 9 December, 2008. Correspondence: Enrique Hong, Department of Pharmacobiology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Czda. de los Tenorios 235, Col. Granjas Coapa, Deleg. Tlalpan, 14330 México DF, México. E-mail: ehong@cinvestav.mx Clin Exp Hypertens Downloaded from informahealthcare.com by Cinvestav on 04/30/10 For personal use only.