Exercise training associated with estrogen therapy induced cardiovascular benefits after ovarian hormones deprivation
Introduction
Heart disease is a major cause of illness and death in women, and its occurrence is increased after menopause [1]. Although the causes of higher cardiovascular morbidity and mortality in postmenopausal women are not well understood, they may involve changes in arterial pressure (AP) and its regulation after estrogen deprivation [2], [3], [4]. Moreover, low arterial baroreflex sensitivity (BRS), a marker of autonomic control, is associated with both higher AP and severity of cardiovascular disease [5], [6].
Despite the description of a number of biologically plausible mechanisms for coronary protection from estrogen, results of well-designed and conducted primary and secondary prevention randomized clinical trials of hormone therapy (HT) documented cardiovascular risk rather than protection [7], [8]. Since the Women's Health Initiative Study [9] has made medical practitioners review the risks and benefits to each patient and made women reconsider the use of HT, according to U.S. Preventive Services Task Force [5], the significance of lifestyle and its impact on cardiovascular function for menopause management are of increasing relevance.
According to the consistent benefits of regular physical exercise to general population [10], a systematic review of randomized controlled trials reported benefits of exercise on metabolic and cardiovascular parameters in postmenopausal women [11]. Recently, we have demonstrated that female ovariectomized (OVX) rats had bradycardia, reduced AP and BRS improvement after 8 weeks of exercise training [12].
Nowadays, the trend is to redirect focus to proved coronary risk reduction interventions for menopausal women, such as smoking cessation, a heart-healthy diet, physical activity, weight management and pharmacologic control of hypertension and hypercholesterolemia [1], [8]. However, the effects of estrogen therapy associated with exercise training are not well known. Therefore, the purpose of the present study was to investigate the effects of HT associated or not with 8 weeks of exercise training in autonomic cardiovascular control in OVX rats.
Section snippets
Animals
Experiments were performed on 35 female virgin Wistar rats (192 ± 4 g) from the Animal Shelter of University of Sao Paulo, Sao Paulo, Brazil, receiving standard laboratory chow and water ad libitum. The animals were housed in individual cages in a temperature-controlled room (22 °C) with a 12-h dark–light cycle. All rats were treated similarly in terms of daily manipulation. All surgical procedures and protocols used were approved by the Experimental Animal Use Committee of the Sao Judas University
Results
Body weight was not different among the groups at the beginning of the protocol. At the end of the protocol, SC group presented lower body weight than SO and TO groups. At the same time, SOE, TO and TOE groups presented reduced body weight in relation to SO group (Table 1).
The aerobic physical performance was similar among groups at the beginning of the experiment and after 4 weeks of training. However, the animals submitted to exercise training (TO and TOE) presented an increase in the maximum
Discussion
In the premenopausal period, the risk of heart disease is considerably lower in women than in men; however, in the postmenopausal period, when estrogen levels are lower, women's risk of heart disease increases dramatically and approaches that of men. In fact, numerous animal studies, using a variety of models, confirm estrogen's cardio-metabolic protective effects [1], [7], [12], [14], [17], [18]. Nowadays, the risks and benefits of HT started to be questioned [19], [20] and the importance of
Competing interest
This paper content has not been published or submitted for publication elsewhere, except as a brief abstract in the proceedings of a scientific meeting. The Ethics Committee of Sao Judas Tadeu has approved the research project (Protocol 01/2008) and the work described in our article was carried out in accordance with EC Directive 86/609/EEC.
Funding
This study was sponsored by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, K.D.A.: 07/57595-5, S.B.: 09/06865-8), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, J.P. and I.C.S.) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, M.C.I.). K.D.A., M.C.I. and F.C.C. are recipients of BPQ fellowships from CNPq.
References (31)
- et al.
Acute administration of 17 beta estradiol improves endothelium-dependent vasodilation in postmenopausal women
Maturitas
(2005) Menopausal hormone therapy and cardiovascular disease
Rev Esp Cardiol
(2006)- et al.
Exercise improves cardiovascular control in a model of dislipidemia and menopause
Maturitas
(2009) - Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the...
- et al.
Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women
Circulation
(2001) - et al.
Estrogen and coronary heart disease in women
JAMA
(1991) - et al.
Epidemiology and risk of hypertension in the elderly: the Framingham Study
J Hypertens
(1988) - Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the...
- et al.
Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators
Lancet
(1998) - Women's Health Initiative. National Institutes of Health;...
Physical exercise and health: a review
Niger J Med
Exercise for health for early postmenopausal women: a systematic review of randomized controlled trials
Sports Med
Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats
Hypertension
Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical stimulation and capsaicin
Headache
Role of exercise training in cardiovascular autonomic dysfunction and mortality in diabetic ovariectomized rats
Hypertension
Cited by (39)
Aerobic or resistance training improves autonomic control of circulation in oophorectomized rats with cardiometabolic dysfunctions: Impact on renal oxidative stress
2021, Experimental GerontologyCitation Excerpt :Moreover, the risk of cardiovascular events in postmenopausal women has been associated with metabolic and cardiovascular changes induced by autonomic dysfunction (Sinagra and Conti, 2007; Kuo et al., 1999; Muka et al., 2016) and metabolic syndrome (Pu et al., 2017). Studies from our group have demonstrated that female rats undergoing ovarian hormone deprivation present increased BP, reduced baroreflex sensitivity and cardiac vagal tone, along with increased sympathetic tone (Irigoyen et al., 2005; Flues et al., 2010). Furthermore, bad eating habits is another factor that contributes to cardiometabolic dysfunction, especially the high consumption of added sugars, which correlates with greater risks of developing cardiometabolic syndrome (CMS) and cardiovascular diseases.
Exercise training initiated at old stage of lifespan attenuates aging-and ovariectomy-induced cardiac and renal oxidative stress: Role of baroreflex
2019, Experimental GerontologyCitation Excerpt :In the present study, even though results did not reach statistical significance, AG-OVX group presented increases of 33% and 13% in adipose tissue and triglycerides, respectively, in comparison to AG rats. It was also shown that ovariectomy in rats may induce an increase in food intake (Latour et al., 2001), which contributes to body weight gain, hypertriglyceridemia, and insulin resistance (Hernandez et al., 2000; Irigoyen et al., 2005; Flues et al., 2010; Machi et al., 2016). Blood pressure increase in ovariectomized rats has been widely reported (Hernandez et al., 2002; Irigoyen et al., 2005; Conti et al., 2015; Machi et al., 2016; da Palma et al., 2016; Shimojo et al., 2018;).
Estradiol ameliorates antioxidant axis SIRT1-FoxO3a-MnSOD/catalase in the heart of fructose-fed ovariectomized rats
2019, Journal of Functional FoodsCitation Excerpt :It should be noticed that fructose overload has been used in animals for inducing metabolic syndrome associated phenotypes (Akar et al., 2012; Cavarape et al., 2001; Conti et al., 2014; Delbosc et al., 2005; Galipeau et al., 2002; Pektas et al., 2015; Rattanavichit et al., 2016; Vasudevan et al., 2005). Furthermore, several studies have used ovariectomy to determine the effects of estrogen deprivation on cardiovascular and metabolic parameters (Bundalo et al., 2015; Campos et al., 2014; Conti et al., 2014; Flues et al., 2010; Rattanavichit et al., 2016). Estradiol administration did not significantly alter energy intake from solid food in fructose-fed rats.
Chronic treatment with angiotensin-converting enzyme inhibitor increases cardiac fibrosis in young rats submitted to early ovarian failure
2017, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :These changes are associated with significant increase of fibrosis (Cabanelas et al., 2012; Felix et al., 2015). In addition, an impairment of the cardiac autonomic control characterized by increased sympathetic participation and/or reduced participation of the vagal tone (Flues et al., 2010). These effects are considered deleterious and emphasize the association of ovarian hormones with the development of cardiac dysfunction (Cavasin et al., 2003; Alecrin et al., 2004; Hinojosa-Laborde et al., 2004; Düzenli et al., 2007; Haines et al., 2012).