ABC | Volume 113, Nº5, November 2019

Original Article Environmental Enrichment Promotes Antioxidant Effect in the Ventrolateral Medulla and Kidney of Renovascular Hypertensive Rats Luiz Eduardo Sous a, I uri Ferrari Del Favero, Frank Silva Bezerr a, A na Beatriz Farias de Souza , Andreia Carvalho Alzamora Universidade Federal de Ouro Preto, Ouro Preto, MG – Brazil Mailing Address: Luiz Eduardo Sousa • Laboratório de Fisiopatologia Experimental (LAFEx), Instituto de Ci ncias Exatas e Biológicas, Departamento de Ci ncias Biológicas - Universidade Federal de Ouro Preto Campus Universitário s/n, Postal Code 35400-000. Morro do Cruzeiro, Ouro Preto, MG – Brasil Email: luizeduardo@ufop.edu.br Manuscript received August 31,2018, revised manuscript December 14, 2018, accepted February 13, 2018. DOI: 10.5935/abc.20190166 Abstract Background: Arterial hypertension is a precursor to the development of heart and renal failure, furthermore is associated with elevated oxidative markers. Environmental enrichment of rodents increases performance in memory tasks, also appears to exert an antioxidant effect in the hippocampus of normotensive rats. Objectives: Evaluate the effect of environmental enrichment on oxidative stress in the ventrolateral medulla, heart, and kidneys of renovascular hypertensive rats. Methods: Forty male Fischer rats (6 weeks old) were divided into four groups: normotensive standard condition (Sham‑St), normotensive enriched environment (Sham-EE), hypertensive standard condition (2K1C-St), and hypertensive enriched environment (2K1C-EE). Animals were kept in enriched or standard cages for four weeks after all animals were euthanized. The level of significance was at p < 0.05. Results: 2K1C-St group presented higher mean arterial pressure (mmHg) 147.0 (122.0; 187.0) compared to Sham-St 101.0 (94.0; 109.0) and Sham-EE 106.0 (90.8; 117.8). Ventrolateral medulla from 2K1C-EE had higher superoxide dismutase (SOD) (49.1 ± 7.9 U/mg ptn) and catalase activity (0.8 ± 0.4 U/mg ptn) compared to SOD (24.1 ± 9.8 U/mg ptn) and catalase activity (0.3 ± 0.1 U/mg ptn) in 2K1C-St. 2K1C-EE presented lower lipid oxidation (0.39 ± 0.06 nmol/mg ptn) than 2K1C-St (0.53 ± 0.22 nmol/mg ptn) in ventrolateral medulla. Furthermore, the kidneys of 2K1C-EE (11.9 ± 2.3 U/mg ptn) animals presented higher superoxide-dismutase activity than those of 2K1C-St animals (9.1 ± 2.3 U/mg ptn). Conclusion: Environmental enrichment induced an antioxidant effect in the ventrolateral medulla and kidneys that contributes to reducing oxidative damage among hypertensive rats. (Arq Bras Cardiol. 2019; 113(5):905-912) Keywords: Renovascular Hypertension; Oxidative Stress; Enviromental Enrichment; Ventrolateral Medulla; Kidney. Introduction Arterial hypertension is a key precursor to the development of stroke, renal failure, heart failure, endothelial dysfunction and cardiovascular disease. Oxidative stress has been implicated in the pathogenesis of arterial hypertension and other cardiovascular diseases. 1,2 Imbalance from excessive oxidative compounds coupled with lowered antioxidant defences induces cellular damage. 1 In hypertensive rats, oxidative stress is linked to heart, kidney, and brain dysfunction. 3-5 Furthermore, reactive oxygen species [ROS] in the ventrolateral medulla are major contributors to sympathetic hyperactivity and arterial hypertension. 4,6 The brainstem contains complex structures that control blood pressure and cardiovascular reflex. 7,8 These regions include the caudal pressor area, caudal ventrolateral medulla (CVLM), and medullocervical pressor area. 7,9 Inhibition and activation of these nuclei cause depressor and pressor responses, respectively. The rostral ventrolateral medulla (RVLM) is an important area of basal sympathetic tone, under regulation by CVLM neurons via tonic and phasic inhibition. 9 Rat studies show that hypertension is associated with lower antioxidant defences and elevated oxidative markers in both CVLM and RVLM. 3,4,6,10 Besides the central nervous system, heart and kidneys are also involved in cardiovascular control. 5 When arterial hypertension develops in renovascular hypertensive rats, both organs experience redox imbalance, along with the increased inflammatory-cell count, lipid peroxidation, and reduced antioxidant defences. 5 A sedentary lifestyle is a risk factor for cardiovascular disease, including arterial hypertension. 11 Physical exercise improves antioxidant defence in the ventrolateral medulla, thus reducing oxidative damage and hypertension. 3,12,13 One way to raise motor activity in laboratory animals is with environmental enrichment. Animals in enriched housing experience neuroanatomical, chemical, and behavioural changes that heighten memory, motor function, sensorial and cognitive activity. 14-16 In turn, neuroplasticity is increased while neurodegenerative disorders and cognitive decline 905