Research Article Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause Anikó Pósa, 1 Renáta Szabó, 1 Anett Csonka, 1 Médea Veszelka, 1 Anikó Magyariné Berkó, 1 Zoltán Baráth, 2 Rudolf Ménesi, 1 Imre Pávó, 1 Mariann Gyöngyösi, 3 Ferenc László, 1 Krisztina Kupai, 1 and Csaba Varga 1 1 Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Kozep Fasor 52, Szeged 6726, Hungary 2 Faculty of Dentistry and Department of Orthodontics and Pediatric Dentistry, University of Szeged, Szeged 6720, Hungary 3 Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria Correspondence should be addressed to Anik´ o P´ osa; paniko@bio.u-szeged.hu Received 25 April 2014; Accepted 4 July 2014 Academic Editor: Narasimham L. Parinandi Copyright © 2015 Anik´ o P´ osa et al. Tis 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. Estrogen defciency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. Te activity and expression of heme oxygenases (HO) in the cardiac lef ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor- (TNF-), the myeloperoxidase (MPO) activity in the cardiac lef ventricle, and the efects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin- protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. Te cardiac HO activity and the expression of HO-1 and HO-2 were signifcantly decreased in the aged rats and afer ovariectomy. Estrogen depletion was accompanied by signifcant increases in the expression of IL-6 and TNF-. Te aged and ovariectomized animals exhibited a signifcantly elevated MPO activity and a signifcant ST segment depression. Afer pretreatment with SnPP augmented ST segment changes were determined. Tese fndings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinfammatory cytokines and biomarkers. 1. Introduction Many epidemiological studies have suggested the involve- ment of free radicals and oxidative stress in aging and certain age-related processes that ofen accompany the menopause [1–3]. An increased level of production of reactive oxygen species (ROS) is considered to be one of the major causes of age-related morbidity (e.g., coronary artery and general cardiovascular dysfunctions) [4]. Estrogen protects women against cardiovascular diseases and seems to play a major role in sex-related diferences in hypertension in experimental models [5]. Antioxidant properties may also be involved since estradiol can reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and increase the expression of superoxide dismutase [6, 7]. Estradiol protects endothelial cells against damage by oxidants and induces the generation of endothelial derived vasodilators, such as nitric oxide (NO) [8]. Recent data indi- cate that another system associated with cardioprotection, the heme oxygenase (HO) system, is also afected by estrogen [9]. HO-1 can catalyze the oxidative degradation of heme to yield equimolar amounts of biliverdin, free iron, and carbon monoxide (CO). Biliverdin is metabolized to bilirubin by biliverdin reductase. Among the products of HO-1, bilirubin and biliverdin are the most potent endogenous scavengers of ROS and CO exerts antiapoptotic and anti-infammatory Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2015, Article ID 429713, 7 pages http://dx.doi.org/10.1155/2015/429713