Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Brazilian Journal of Medical and Biological Research (2015) 48(11): 1010–1022, http://dx.doi.org/10.1590/1414-431X20154499 ISSN 1414-431X Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats R.C.A. Maia2*, L.E. Sousa1,3*, R.A.S. Santos4, M.E. Silva2,3, W.G. Lima1,2,3, M.J. Campagnole-Santos4 and A.C. Alzamora1,2,3 1 Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil 2 Programa de Pós-Graduac¸ão em Saúde e Nutric¸ão, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brasil 3 Programa de Pós-Graduac¸ão em Ciências Biológicas, NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil 4 Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil Abstract Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension. Key words: 2K1C renovascular hypertension; Swimming; Baroreflex bradycardia; Heart and kidney adaptations; Oxidative stress Introduction Structural and functional alterations in the heart and kidney are involved in the development of arterial hypertension by hyperactivity of the sympathetic nervous system and renin-angiotensin system (RAS) as well as their contributions to high blood pressure and reduced sensitivity of the baroreflex control of the heart rate (HR) (1,2). Many studies (1–4) have used the two-kidney, oneclip (2K1C) Goldblatt hypertensive model in an attempt to understand the mechanisms of development and maintenance of renovascular hypertension. The time course of the 2K1C hypertensive model has been divided into several phases after clipping of the renal artery: at about 4 weeks, blood pressure rises in association with increases in the plasma renin activity and circulating angiotensin II (Ang II) concentration. In weeks 5 to 8, hypertension is associated with increases in tissue RAS components despite a fall in plasma renin activity and circulating Ang II. At week 9 and after, hypertension is maintained by increases in the tissue RAS activity, plasma volume, and sympathetic tone (1). Moreover, evidence has shown increased generation of reactive oxygen species (ROS) in specific organs such as the brain, heart, and kidneys during renovascular hypertension (3,4). Correspondence: A.C. Alzamora: <>. *R.C.A. Maia and L.E. Sousa are co-first authors. Received November 15, 2014. Accepted April 22, 2015. First published online August 11, 2015. Braz J Med Biol Res 48(11) 2015 www.bjournal.com.br Swimming decreases oxidative stress in 2K1C rats over time Ang II, aldosterone, and catecholamines are involved in the development of ventricular hypertrophy under pathological (5,6) and physiological (7,8) conditions, reflected as worsening or improvement of cardiac function, respectively. Ventricular hypertrophy can be concentric in certain pathological conditions, such as arterial hypertension, or concentric and eccentric in physiological cardiac hypertrophy induced by static or dynamic physical exercise training (Ex), which induces two different types of intermittent chronic cardiac workload (6,8,9). Ex induces adaptive cardiovascular benefits in hypertensive conditions by reducing the sympathetic outflow, vascular resistance, and plasma Ang II levels and improving the sensitivity of the baroreflex (2,10–13). Additionally, during endurance Ex, the increase in oxygen consumption results in increased generation of ROS, which is involved in the adaptive up-regulation of antioxidant gene expression (14). Moreover, evidence has shown that low-intensity Ex (50–60% of maximal exercise capacity) more effectively decreases blood pressure in hypertensive patients and rats than does high-intensity Ex (7,15–17). However, to maintain these benefits over time, close monitoring by healthcare professionals is required to adjust the Ex intensity to avoid possible adverse effects of more vigorous exercise, especially in hypertensive states, considering that risk factors such as age and cardiac disease could be associated with this pathology (18–20). In the present study, our hypothesis was that Ex performed without adjusting the workload over time, even if it does not effectively reduce the blood pressure, could have beneficial effects on organs that participate in the control of blood pressure and thus reduce the cardiovascular risk. In view of these considerations, we evaluated the time-course effects of Ex without workload on the mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress at different stages of development of 2K1C hypertension. Material and Methods Ethics approval All experiments were performed on 123 male Fischer rats (10 weeks of age; 150–180 g) from ENUT, Universidade Federal de Ouro Preto, MG, Brasil. The animals were housed in separate cages in groups of four (2K1C or SHAM) with free access to rat chow and tap water in a temperature- and light-controlled room (24±1°C; 12:12 h light-dark cycle). All animal procedures were in accordance with the Guidelines for Ethical Care of Experimental Animals and performed as approved by the Institutional Ethics Committee of the Universidade Federal de Ouro Preto (Protocol #022/2007). www.bjournal.com.br 1011 Induction of renovascular hypertension Renovascular hypertension was induced as described by Goldblatt et al. (21). Briefly, the rats wer (...truncated)