ABC | Volume 111, Nº2, August 2018

Original Article Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats Joel Alves Rodrigues, 1 Thales Nicolau Prímola-Gomes, 1 Leôncio Lopes Soares, 1 Tiago Ferreira Leal, 1 Clara Nóbrega, 2 Danillo Laviola Pedrosa, 1 Leonardo Mateus Teixeira Rezende, 1 Edilamar Menezes de Oliveira, 2 Antonio Jose Natali 1 Universidade Federal de Viçosa (UFV), 1 Viçosa, MG - Brazil Universidade de São Paulo (USP), 2 São Paulo, SP - Brazil Mailing Address: Joel Alves Rodrigues • Rua Ana koester, 65 AP 302. Postal Code 36570-000, Centro, Viçosa, MG – Brazil E-mail: joel.a.rodrigues1@gmail.com, joel.rodrigues@ufv.br Manuscript received September 27, 2017, revised manuscript March 15, 2018, accepted April 11, 2018 DOI: 10.5935/abc.20180113 Abstract Background: Regulation of intracellular calcium (Ca 2+ ) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca 2+ ) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups –sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca 2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca 2+  transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca 2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility. (Arq Bras Cardiol. 2018; 111(2):172-179) Keywords: Hypertension; Exercise; Rats; Calcium Signaling; Intracellular Calcium; Sensing Proteins. Introduction Sustained systemic arterial hypertension causes progressive myocardial remodeling. While cardiac function is increased in response to active myocyte hypertrophy in the left ventricle in the compensated phase, left ventricular (LV) remodeling is characterized by the combination of cardiomyocyte hypertrophy and proliferation of other tissues. For example, collagen deposition result in fibrosis of ventricular tissue and consequent myocardial stiffness. 1,2 This has been reported in the initial compensatory phase of hypertension (3‑4 months), with preservation of cardiac function. 1 Increased proinflammatory markers (e.g. IL-6; TNF- α ) have been found in the left ventricle of spontaneously hypertensive rats (SHR) as young as 5-6 months. 3,4 The benefits of aerobic training to hypertensive subjects are well established in the literature. 5,6 Animal models of hypertension – SHR in the compensated stage (~ 6-month‑old) – have shown the efficacy of this type of training in attenuating systolic dysfunction and restoring ventricular elasticity in female SHR. 7 Aerobic training reduced apoptosis in the myocardium of SHR, 4,8 improved contractile function of cardiomyocytes isolated from the left ventricle, and normalized the expression of proteins involved in the regulation of intracellular calcium cycle, such as the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban. 9-11 In physiological or pathological cardiac hypertrophy, expression of microRNAs (miRNAs) related to cardiac remodeling is altered. 12 MicroRNA 214 (miR-214) is involved in cardiac muscle contraction and Ca 2+ sequestration, due to its negative effect on SERCA-2a expression. 13 With respect to physical exercise, resistance training improved cardiomyocyte contractile function, with increased expression of SERCA2a and decreased miRNA-214 expression in normotensive, infarcted rats. 13,14 However, little is known about miR-214 expression in SHR subjected to aerobic training. Thus, the aim of this study was to evaluate the effects of aerobic training on cardiomyocyte contractility and miR-214 expression in the left ventricle in hypertensive rats. 172