The endothelium is considered an active and dynamic tissue with important properties such as maintenance of blood circulation, regulation of vascular tone, microvascular permeability, signaling, and vascular angiogenesis and inflammatory response.¹1 Kiseleva RY, Glassman PM, Greineder CF, Hood ED, Shuvaev VV, Muzykantov VR. Targeting therapeutics to endothelium: Are we there yet? Drug Deliv Transl Res. 2018;8(4):883-902. The endothelium allows the connection among components of the circulation and body systems. Endothelial cells produce and, depending on the stimulus received, release factors that lead to vascular smooth muscle cells contraction or relaxation.²2 Persson PB. The multiple functions of the endothelium: More than just wallpaper. Acta Physiol. 2015;(4)213:747-9. Vascular tone control by the endothelium is modulated by the production and release of mediators such as nitric oxide, prostacyclins, prostaglandins, thromboxane, angiotensin II, endothelin-1 and reactive oxygen species. Under physiological conditions, these factors are balanced. Imbalance in the production of substances by the endothelium leads to triggering and progression of several conditions and diseases such as ischemia, thrombosis, atherosclerosis, arterial hypertension, inflammation and tumor growth.¹1 Kiseleva RY, Glassman PM, Greineder CF, Hood ED, Shuvaev VV, Muzykantov VR. Targeting therapeutics to endothelium: Are we there yet? Drug Deliv Transl Res. 2018;8(4):883-902.^,22 Persson PB. The multiple functions of the endothelium: More than just wallpaper. Acta Physiol. 2015;(4)213:747-9. Therefore, vascular endothelial dysfunction is an important pathophysiological factor in human diseases.³3 Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057-69.

Endothelial dysfunction is mainly characterized by changes in endothelial actions involving the reduction of vasodilation and the induction of a pro-inflammatory or prothrombotic state.³3 Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057-69. Due to its clinical importance, endothelial dysfunction is considered an independent predictor of cardiovascular risk. In addition, it can also be observed in non-cardiovascular diseases, such as rheumatic and autoimmune diseases.²2 Persson PB. The multiple functions of the endothelium: More than just wallpaper. Acta Physiol. 2015;(4)213:747-9.

Among the substances produced by the endothelium, nitric oxide stands out, being a potent modulator of vascular and cardiac function. Insufficient production of nitric oxide, such as in aging and in several diseases, may result in an increase in reactive oxygen species and blood pressure, and adversely affects the physical capacity and health in general.²2 Persson PB. The multiple functions of the endothelium: More than just wallpaper. Acta Physiol. 2015;(4)213:747-9.

Physical exercises have been advocated for the promotion of health and the non-pharmacological treatment of cardiovascular diseases. Regular practice of exercises results in numerous health benefits, such as improvement in body composition, physical capacity, insulin resistance, endothelial function, arterial hypertension, antioxidant status, quality of life,⁴4 Rodrigues AC, Natali AJ, Cunha DNQD, Costa AJLD, Moura AG, Araújo Carneiro-Júnior M, et al. Moderate continuous aerobic exercise training improves cardiomyocyte contractility in β1 adrenergic receptor knockout mice. Arq Bras Cardiol. 2018;110(3):256-62.

5 Winter SCN, Macedo RM, Francisco JC, Santos PC, Lopes APS, Meira LF, et al. Impact of a high-intensity training on ventricular function in rats after acute myocardial infarction. Arq Bras Cardiol. 2018;110(4):373-80.

6 Lemos MP, Mota GRD, Marocolo M, Sordi CC, Chriguer RS, Barbosa Neto O. Exercise training attenuates sympathetic activity and improves morphometry of splenic arterioles in spontaneously hipertensive rats. Arq Bras Cardiol. 2018;110(3):263-9.

7 Martinez JE, Taipeiro EF, Chies AB. Effects of continuous and accumulated exercise on endothelial function in rat aorta. Arq Bras Cardiol. 2017;108(4):315-22.

8 Gomes MFP, Borges ME, Rossi VA, Moura EOC, Medeiros A. The effect of physical resistance training on baroreflex sensitivity of hypertensive rats. Arq Bras Cardiol. 2017;108(6):539-45.

9 Gomes MJ, Martinez PF, Campos DHS, Pagan LU, Bonomo C, Lima AR, et al. Beneficial effects of physical exercise on functional capacity and skeletal muscle oxidative stress in rats with aortic stenosis-induced heart failure. Oxid Med Cell Longev. 2016;2016:8695716.

10 Pagan LU, Damatto RL, Cezar MD, Lima AR, Bonomo C, Campos DH, et al. Long-term low intensity physical exercise attenuates heart failure development in aging spontaneously hypertensive rats. Cell Physiol Biochem. 2015;36(1):61-74.

11 Gomes MJ, Martinez PF, Pagan LU, Damatto RL, Cezar MD, Lima AR, et al. Skeletal muscle aging: Influence of oxidative stress and physical exercise. Oncotarget. 2017;8(12):20428-40.^-1212 Ghorbanzadeh V, Mohammadi M, Dariushnejad H, Abhari A, Chodari L, Mohaddes G. Cardioprotective effect of crocin combined with voluntary exercise in rat: Role of mir-126 and mir-210 in heart angiogenesis. Arq Bras Cardiol. 2017;109(1):54-62. and an important effect on the endothelial system. During its practice, increased blood flow and shear stress improve vascular homeostasis by reducing the production of reactive oxygen species, and increasing the availability of nitric oxide in the endothelium.¹³13 Durand MJ, Gutterman DD. Exercise and vascular function: How much is too much? Can J Physiol Pharmacol. 2014;92(7):551-7.

Because endothelial function and physical exercise have an important interface with cardiovascular diseases, we consider the review of this area in articles recently published by the Arquivos Brasileiros de Cardiologia in the Basic and Experimental Research Area relevant. In this Editorial, we have commented on three articles that have been published in the last two years, and which are related to endothelial changes from physical exercise, both in healthy rats and in spontaneously hypertensive rats.

Mota et al.¹⁴14 Mota MM, Silva TLTBD, Macedo FN, Mesquita TRR, Quintans LJJ, Santana-Filho VJ, et al. Effects of a single bout of resistance exercise in different volumes on endothelium adaptations in healthy animals. Arq Bras Cardiol. 2017;108(5):436-42. observed that a single resisted exercise session improves the endothelial function, and increases nitric oxide synthesis in both the endothelium and the smooth muscle layer of healthy rats. As a parameter of vascular reactivity, endothelium-dependent vasodilation in the mesenteric artery was evaluated. Exercise practice increased insulin-induced vasodilation. As vascular relaxation was abolished by the nitric oxide synthesis inhibitor, the methyl ester of L'NG-nitro-arginine (L-NAME), the importance of nitric oxide in the vasodilator response was enhanced. According to the authors, exercise stimulates factors that increase the production of nitric oxide, such as vascular distension, catecholamine release and intermittent hypoxia. The increase in nitric oxide production was dependent on the volume of exercise, which suggests that a greater demand of oxygen and nutrients is involved in the beneficial effects of exercise on the endothelium.

Similar results were observed in hypertensive rats.¹⁵15 Faria TO, Angeli JK, Mello LGM, Pinto GC, Stefanon I, Vassallo DV, et al. A single resistance exercise session improves aortic endothelial function in hypertensive rats. Arq Bras Cardiol. 2017;108(3):228-36. A single session of resisted exercise provided the activation of endothelial nitric oxide synthase (eNOS), increased acetylcholine-induced aortic relaxation, and decreased reactivity to phenylephrine. The response to phenylephrine was abolished by L-NAME. Therefore, data reinforce that, even in arterial hypertension, the improvement of the endothelial function induced by a single session of resisted exercise is associated with the increase of nitric oxide synthesis.

Beneficial results were also observed after a long period of exercise (one hour/day on treadmill, 5 days a week, 8 weeks) in healthy rats.⁷7 Martinez JE, Taipeiro EF, Chies AB. Effects of continuous and accumulated exercise on endothelial function in rat aorta. Arq Bras Cardiol. 2017;108(4):315-22. Martinez et al.⁷7 Martinez JE, Taipeiro EF, Chies AB. Effects of continuous and accumulated exercise on endothelial function in rat aorta. Arq Bras Cardiol. 2017;108(4):315-22. observed that exercise reduced the contractile response of the aorta to noradrenaline and increased the relaxation induced by acetylcholine. On the other hand, the accumulated exercise protocol (four periods of 15 minutes per day on treadmill, 5 times per week, 8 weeks) did not result in improvement of endothelial function. Consequently, it is believed that the beneficial effects on the induction of regulatory factors that improve endothelial function are linked to the time of exercise exposure.

These experimental studies suggest that the practice of physical exercises plays a relevant role in the treatment of endothelial dysfunction. However, additional studies are needed to establish the best type, intensity and duration of exercise, and to allow more efficient prescribing.

Acknowledgments

Funding by the National Council for Scientific and Technological Development (CNPq) (Proc. No. 308674 / 2015-4) and São Paulo Research Foundation (FAPESP) (Proc. N°. 2014 / 23592-3 and 2014 / 00747-1).

References

Publication Dates

History