Research Article Lifestyle-Induced Redox-Sensitive Alterations: Cross-Talk among the RAAS, Antioxidant/Inflammatory Status, and Hypertension Renáta Szabó , 1,2 Denise Börzsei , 1 Alexandra Hoffmann , 1,3 Zelma Nadin Lesi, 1 Rudolf Gesztelyi , 4 Béla Juhász , 4 Gábor J. Szebeni , 1,5 Jasmin Osman, 1 Judith Sebestyén, 6 Arnold Nagy, 1,7 Sándor Szegedi, 1,7 Csaba Varga , 1,3 and Anikó Pósa 1,2 1 Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H-6726, Hungary 2 Interdisciplinary Excellence Centre, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary 3 HR-Pharma Ltd., Szeged, Hungary 4 Department of Pharmacology and Pharmacotherapy, University of Debrecen, H-4032 Debrecen, Hungary 5 Laboratory of Functional Genomics, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged H-6726, Hungary 6 South-Pest Hospital Centre, National Institute for Infectology and Haematology, Department of Burns and Plastic Surgery, Budapest H-1097, Hungary 7 NAGYKUN-HÚS Ltd., Kunhegyes, H-5340, Hungary Correspondence should be addressed to Anikó Pósa; paniko@bio.u-szeged.hu Received 2 July 2021; Accepted 29 September 2021; Published 25 October 2021 Academic Editor: Simon Lees Copyright © 2021 Renáta Szabó 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. The development and progression of hypertension are closely linked to an unhealthy lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the effects of diet and exercise on the elements of the renin–angiotensin–aldosterone system (RAAS), redox-sensitive parameters, and the expression of the vascular tone regulator endothelial nitric oxide synthase (eNOS). Male control Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats were randomized based on the type of diet (standard chow, high-fat diet: HT, and fructose-enriched diet: HF) and exercise (voluntary wheel-running exercise or lack of exercise). After 12 weeks of experimental period, the concentrations of the RAAS elements, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) concentrations, levels of superoxide dismutase (SOD) and glutathione (GSH), and expressions of extracellular signal-regulated kinase1/2 (ERK1/2) and phosphorylated ERK1/2 as well as eNOS were measured in the cardiac tissue of WKY and SHRSP rats. We found that the RAAS elements were overactivated under hypertension and were further elevated by HT or HF diet, while HT and HF diet enhanced MPO and TNF-α parameters as well as the expression of pERK1/2; SOD, GSH, and eNOS levels were decreased. These changes occurred in WKKY rats and reached the statistically significant level in SHRSP animals. 12 weeks of exercise compensated the adverse effects of HT and HF via alleviating the concentrations of the RAAS elements and inflammatory markers as well as increasing of antioxidants. Our findings prove that SHRSP rats are more vulnerable to lifestyle changes. Both the type of diet and exercise, as a nonpharmacological therapeutic tool, can have a significant impact on the progression of hypertension. 1. Introduction Growing evidence indicates that oxidative stress caused by overproduction of reactive oxygen species (ROS) plays a crucial role in the development of cardiovascular diseases (CVDs), such as hypertension, arrhythmias, and coronary ischemia [1, 2]. ROS accumulation mediates various signal- ing pathways, which promote redox imbalance as well as disruption of the vascular tone regulation [3]. A number of studies revealed a very close relationship between oxidative stress and overactivation of the renin–angiotensin–aldoste- rone system (RAAS) [4]. Abnormal activity of the RAAS Hindawi Oxidative Medicine and Cellular Longevity Volume 2021, Article ID 3080863, 13 pages https://doi.org/10.1155/2021/3080863