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Peptides 47 (2013) 29–35

Contents lists available at ScienceDirect

Peptides

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wimming training prevents fat deposition and decreases angiotensinI-induced coronary vasoconstriction in ovariectomized rats

atrick Wander Endlicha,b,∗, Erick Roberto Gonc alves Claudioa,ashington Luiz da Silva Gonc alvesa, Sonia Alves Gouvêaa, Margareth Ribeiro Moysésa,

laucia Rodrigues de Abreua

Department of Physiological Sciences, Health Sciences Center, Federal University of the Espírito Santo, Vitória, Espírito Santo, BrazilCatholic Faculty Salesiana of the Espírito Santo, Vitória, Espírito Santo, Brazil

r t i c l e i n f o

rticle history:eceived 13 May 2013eceived in revised form 31 May 2013ccepted 3 June 2013vailable online 19 June 2013

eywords:strogen deficiencyoronary dysfunctionAShysical exercise

a b s t r a c t

We investigated the effects of chronic swimming training (ST) on the deposition of abdominal fat andvasoconstriction in response to angiotensin II (ANG II) in the coronary arterial bed of estrogen deficientrats. Twenty-eight 3-month old Wistar female rats were divided into 4 groups: sedentary sham (SS),sedentary-ovariectomized (SO), swimming-trained sham (STS) and swimming-trained ovariectomized(STO). ST protocol consisted of a continuous 60-min session, with a 5% BW load attached to the tail, com-pleted 5 days/week for 8-weeks. The retroperitoneal, parametrial, perirenal and inguinal fat pads weremeasured. The intrinsic heart rate (IHR), coronary perfusion pressure (CPP) and a concentration–responsecurve to ANG II in the coronary bed was constructed using the Langendorff preparation. Ovariectomy(OVX) significantly reduced 17-�-estradiol plasma levels in SO and STO groups (p < 0.05). The STO grouphad a significantly reduced retroperitoneal and parametrial fat pad compared with the SO group (p < 0.05).IHR values were similar in all groups; however, baseline CPP was significantly reduced in the SO, STS and

STO groups compared with the SS group (p < 0.05). ANG II caused vasoconstriction in the coronary bed ina concentration-dependent manner. The SO group had an increased response to ANG II when comparedwith all other experimental groups (p < 0.05), which was prevented by 8-weeks of ST in the STO group(p < 0.05). OVX increased ANG II-induced vasoconstriction in the coronary vascular bed and abdominal fatpad deposition. Eight weeks of swimming training improved these vasoconstrictor effects and decreased

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abdominal fat deposition

. Introduction

Menopause is a risk factor for many cardiovascular diseases

CVD). Estrogen deficiency is also known to impair cardiovascu-ar function and metabolism [54]. The incidence of cardiovascularisease is 4-fold higher in post-menopausal women compared with

Abbreviations: ACE, angiotensin-converting enzyme; ANG II, angiotensin II;NOVA, analysis of variance; BW, body weight; CAD, coronary artery disease; CPP,oronary perfusion pressure; CVD, cardiovascular diseases; HRT, hormone replace-ent treatment; ING, inguinal; IHR, intrinsic heart rate; NO, nitric oxide; OVX,

variectomy; PME, parametrial; PR, perirenal; RAS, Renin Angiotensin System; RET,etroperitoneal abdominal adiposity; ROS, reactive oxygen species; SO, sedentaryvariectomized; SS, sedentary sham; ST, swimming training; STO, swimming-rained ovariectomized; STS, swimming-trained sham; UT, uterus weight.∗ Corresponding author at: Laboratório de Regulac ão Neuro-Humoral dairculac ão, Departamento de Ciências Fisiológicas, Universidade Federal do Espiritoanto, Avenida Marechal Campos, 1468, Bairro Maruípe, CEP: 29040-755, Vitoria –S, Brazil. Tel.: +55 273335 7473; fax: +55 273335 7330.

E-mail address: patrickwe@hotmail.com (P.W. Endlich).

196-9781/$ – see front matter © 2013 Elsevier Inc. All rights reserved.ttp://dx.doi.org/10.1016/j.peptides.2013.06.002

ariectomized rats.© 2013 Elsevier Inc. All rights reserved.

women of the same age who are pre-menopausal [30]. A key sys-tem for cardiovascular control is the Renin Angiotensin System(RAS). It is well recognized that the RAS is susceptible to modula-tion by estrogen [7]. Clinical [39,48] and animal [25,37,53] studieshave indicated an inverse association between estrogen and theactivation of the RAS. Increases in the circulating levels of ANG IIand dysregulation (upregulation or activation) of the vasoconstric-tor arm of the RAS have been implicated in many CVDs, includingcoronary artery disease (CAD). Several studies have suggested thatestrogen has modulatory effects on angiotensin II receptors expres-sion, as the decrease in the expression of AT1 receptor in variousorgans [14,37]. Conversely, Baiardi et al. have shown that estro-gen causes an upregulation of both ANG II receptors in female ratkidneys [4]. Moreover, estrogen can modify other compounds ofthe RAS, such as circulating angiotensinogen [11,48], plasma reninactivity [5,59] or concentration [8], serum angiotensin-converting

enzyme (ACE) activity [5,8], ANG I [5], ANG II [8], or plasma andtissue ACE activity [5,8,14,18].

Another risk factor for developing CVD is the increase in adi-pose tissue. Estrogen has been recognized as an important regulator

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f female adipose tissue development and deposition in humans,odents and other species [31]. After menopause, estrogen insuffi-iency is thought to be largely responsible for the redistribution ofat to the upper body [19]. In addition, there are reports showinghat estrogen deficiency decreases lipolysis in adipose tissue [13].n the other hand, the estrogen replacement therapy prevents theentral fat distribution [19] as well as decreases fatty acid synthesisnd increases the lipolysis rate [23], which indicates a direct actionf estrogen in fat cells.

Numerous epidemiological studies have convincingly shownhat physical exercise has a beneficial effect on cardiovascular dis-ase outcomes. Exercise reduces heart rate and blood pressure,ugments myocardial oxygen uptake, and regulates circulatinglood volume as well as various metabolic processes. Accordingo reports of the consistent benefits of regular physical exerciseo the general population [2], a systematic review of randomizedontrolled trials reported benefits of exercise on metabolic and car-iovascular parameters in post-menopausal women [3]. However,lthough most studies have investigated the role of exercise in theondition of estrogen deficiency, such as occurs in menopause, fewtudies have reported the role of physical exercise on the RAS inhe cardiovascular system. In a study conducted by Habouzit et al.,emale rats were submitted to chronic running training, and nohanges in the activity of plasma or muscle ACE were found [20].nother study showed that the involvement of the RAS in left ven-

ricular hypertrophy was induced by swimming training in femaleats [40]. In Wistar rats, the practice of chronic training or acuteunning session promotes the attenuation of the vasoconstrictoresponse to Ang II in aorta artery segments in an endothelium-ndependent process [27], as well as in the femoral veins [10].

It was previously demonstrated that exercise training invariectomized rats decreases fat deposition which has only beennvestigated in a limited number of studies that evaluated theffects of running training [46]; however, the effects of swimmingraining remain to be determined. Thus, we analysed if the practicef chronic swimming training is able to maintain the visceral fatistribution in a similar pattern observed in animals with normalstrogens levels.

Moreover, CAD is the most prevalent cardiovascular disease inost-menopausal women and can lead to death [55]. Nevertheless,

ittle is known about the relationship between exercise and coro-ary vascular reactivity in female OVX rats. Therefore, we testedhe hypothesis that exercise training could modulate the vasocon-trictor response promoted by ANG II (the main vasoconstrictor ofhe RAS) in the coronary bed of rats submitted to ovariectomy.

Rodents become anovulatory at a mature age (10–12 monthsld) but maintain a basal gonadal steroid secretion, in contrast tohat happens in women. Accordingly, ovariectomy in those ani-als became the best tool to mimic human ovarian hormone loss

36].

. Methods

.1. Experimental groups and animal care

Female 3-month-old Wistar rats weighing between 280 and00 g from the university facility were used in this study. All pro-edures were approved by the Institutional Ethical Committee fornimal Care and Use of the Federal University of Espírito Santo.xperiments were conducted in accordance with the Guide for theare and Use of Laboratory Animals published by the US National

nstitutes of Health (NIH Publication, revised 1996), and effortsere made to minimize animal suffering. The animals were kept

n collective cages with free access to water and standard rathow (Purina Labina®, SP, Brazil) under a controlled temperature

es 47 (2013) 29–35

(22–24 ◦C), humidity (40–60%) and light–dark cycle (12–12 h). Atthe time of ovariectomy, the animals were divided randomly intothe following 4 groups: sedentary sham (SS, n = 7), sedentary-ovariectomized (SO, n = 7), swimming-trained sham (STS, n = 7), andswimming-trained-ovariectomized (STO, n = 7).

2.2. Ovariectomy

Ovariectomy was performed under general anesthesia withintraperitoneal injections of ketamine (80 mg/kg) and xylazine(12 mg/kg). A bilateral dorsolateral incision was made through theskin and the underlying muscle was dissected to locate the ovaryand fallopian tube. The fallopian tube was ligated with a suture lineand the ovary was removed. The muscle and skin were then suturedwith an absorbable suture. After the surgery, animals received anintramuscular injection of antibiotic (2.5% enrofloxacin, 0.1 mL).In sham-operated animals, surgery, but no ovariectomy was per-formed. All animals underwent surgery in the same period andstarted swimming training thirty days after surgery. The trainingprotocol was started at this time to evaluate the role of physi-cal training in reversing or decreasing the harmful effects of theestrogen deficiency.

2.3. Swimming training

Exercise training was performed in a swimming pool(180 cm × 70 cm × 60 cm) filled with tap water warmed to approx-imately 30–32 ◦C at the same time of day (14:00–16:00 pm) in alltraining sessions during 8 weeks. The exercise intensity was pro-gressively increased over the first two weeks. In the first day, therats swam for 10 min, and swim time was increased until the ratswere swimming for thirty minutes on the fifth day. In the secondweek, the swim time was increased each day until the animals couldswim for 60 min while wearing a caudal dumbbell, weighing 5% oftheir body weight (overload) [43]. This protocol has previously beencharacterized as low to moderate intensity (with a long duration)based on improvements in muscle oxidative capacity [33].

2.4. Isolated heart preparation

The coronary function of rats was evaluated using the Langen-dorff preparation (Hugo Sachs ElectronicsTM, March-Hugstetten,Germany). Forty-eight hours after the last exercise session, theanimals were killed by decapitation. After decapitation, their tho-rax was opened and the hearts were rapidly excised and placedin ice-cold modified Krebs buffer. The aorta was immediately can-nulated with a 21 G needle and perfused with a modified Krebsbuffer (composed of 120 mM NaCl, 1.26 mM CaCl2·2H2O, 5.4 mMKCl, 2.5 mM MgSO4·7H2O, 2 mM NaH2PO4·H2O, 27 mM NaHCO3,1.2 mM Na2SO4, 0.03 mM EDTA, and 11 mM glucose). The Krebsbuffer was equilibrated with a carbogen mixture (O2 95% + CO2 5%,White-Martins Ind., RJ, Brazil) at a constant pressure of 100 mmHgto give a pH of 7.4 and kept at 37 ◦C. The perfusion flow was main-tained at a rate of 10 mL/min by a peristaltic pump (MS-Reglo4-channel, Hugo Sachs ElectronicsTM), according to the Langendorffmethods [35,47].

After a small surgical incision in the left atrium, isovolumet-ric cardiac pressure was recorded with a water-filled latex balloon(Durex, London, UK) inserted into the left ventricle (LV) througha steel catheter connected to a transducer (TPS-2 Statham trans-ducer – Incor, Sao Paulo, SP, Brazil). The LV end-diastolic pressurewas set at 8–10 mmHg by adjusting the balloon volume through a

spindle syringe. The coronary perfusion pressure (CPP) and intrinsicheart rate (IHR) were continuously recorded with a sidearm of theaortic cannula with a pressure transducer (P23Db Statham trans-ducer – Incor, Sao Paulo, SP, Brazil) connected to data acquisition

Peptides 47 (2013) 29–35 31

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Fig. 1. Estrogenic status of female rats. (A) Plasma levels of estradiol and (B) uter-ine wet weight in sedentary sham (SS, n = 7), sedentary ovariectomized (SO, n = 7),swimming-trained sham (STS, n = 7) and swimming-trained ovariectomized (STO,n = 7) groups. Data are expressed as the mean ± SEM. A one-way ANOVA with Tukey’spost hoc test was used. *p < 0.05 vs. SS group, #p < 0.05 vs. STS group.

Table 1Effects of ovariectomy (OVX) and swimming training (ST) on body weight in femalerats.

Data SS SO STS STO

Body weight (g)1st wk 297 ± 4 294 ± 3 301 ± 5 298 ± 38th wk 374 ± 5d 393 ± 3a,d 308 ± 3b 343 ± 6a,c

% range 20 26 2 13

Data are expressed as the mean ± SEM for each of the following groups: seden-tary sham (SS, n = 7), sedentary-ovariectomized (SO, n = 7), swimming-trained sham(STS, n = 7) and swimming-trained-ovariectomized (STO, n = 7). One-way ANOVAwith Tukey’s post hoc test were used.

a p < 0.05 vs. the SS group.

P.W. Endlich et al. /

ystem (PowerLabTM, ADI Instruments, Bela Vista, NSW, Australia).fter a stabilization period of 40 min, baseline values of CPP and

HR were determined. Then, the responsiveness of the coronaryascular bed was evaluated. A bolus injection (100 �l) of modifiedrebs’s buffer was applied to determine volume-injection-inducedhanges in CPP and IHR. Subsequently, concentration–responseurves to ANG II (a concentration range in the injection fluid of.001–1000 ng, Sigma–Aldrich, USA) were constructed by applying

n bolus injections (100 �l) in the coronary bed at 10 min intervals.

.5. Plasma 17ˇ-estradiol concentrations

After decapitation, blood samples were collected in sterile tubesontaining EDTA/K3, centrifuged at 3000 × g for 15 min at 4 ◦CFanem, São Paulo, Brazil) and stored at −80 ◦C until use. Plasma7�-estradiol concentrations were analyzed by an electrochemi-

uminescence immunoassay method (Elecsys 2010, Roche, Basel,witzerland), with available kits (Estradiol II, Roche, Mannheim,ermany).

.6. Bilateral lipectomia

The measures for right and left retroperitoneal abdominal adi-osity (RET) and perirenal (PR), parametrial (PME), and inguinalING) adiposities were determined by means of bilateral lipectomythe surgical extraction of fat pads). A longitudinal incision of ±6 cmas made on the abdominal skin using the Alba line as a reference.ext, the ING compartments were mechanically collected and mea-

ured and the peritoneum was cut open, and the RET, PR and PMEat pads were taken out following a similar protocol reported byhi et al. [49].

.7. Statistical analysis

The nature of the variables studied or the variability of the meansas assessed by biostatistics software Prism 5.0 (Graph-PadTM Inc.,

an Diego, CA, USA). Data are expressed as the mean ± SEM. Datarom 17-�-estradiol levels, body fat and uterine weight as wells CPP and IHR were analyzed by one-way analysis of varianceANOVA), with physical training considered as the main factor. TheNG II-induced vasoconstriction was analyzed using a two-wayNOVA, with physical training and the concentrations of ANG IImployed were considered the main factors. In both cases, the dif-erences among groups were determined by Tukey’s post hoc testor multiple comparisons. Statistical significance was set at p < 0.05.

. Results

.1. Surgery efficacy

Plasma 17�-estradiol concentration and the uterus weight (UW)ere used to determine the estrogenic status. As expected, thereas a significant decrease in both of these parameters in OVX ani-als (p < 0.05) when compared with the SS and STS groups (Fig. 1A

nd B).

.2. Body composition analysis

Table 1 shows the body weight (BW) at the beginning and end ofhe study. There were no differences in BW among all groups beforehe experimental period; however, all groups, except for the STS

roup, had an increased BW after the experimental period (p < 0.05).ig. 2 shows the fat pad values. The RET and PME fat pad weight inTO group was significantly less than the SO group (p < 0.05). In theET and PME fat pad weight in STS group was significantly less than

b p < 0.01 vs. the SS group.c p < 0.05 vs. the 1st week.d p < 0.01 vs. the 1st week.

the SS group (p < 0.05), demonstrating the efficacy of ST in reducingadiposity. Moreover, the SO group showed an increased RET andPME fat pad weight compared with the SS group (p < 0.05). The PRvalues did not change among the groups tested. The inguinal fatpad was increased in both ovariectomized groups compared withthe SS group (p < 0.05); however, the inguinal fat pad in the STOgroup was also increased compared with the STS group (p < 0.05).

3.3. Coronary perfusion pressure and reactivity to ANG II

The IHR (Fig. 3A) was similar in all groups. Baseline CPP wassignificantly lower (p < 0.05) in the SO, STS and STO groups whencompared with the SS group (91 ± 9 mmHg), as shown in Fig. 3B.

32 P.W. Endlich et al. / Peptides 47 (2013) 29–35

Fig. 2. Effects of swimming training on the (A) retroperitoneal, (B) perirenal, (C) parametrial and (D) inguinal fat pads in sedentary sham (SS, n = 7), sedentary ovariectomized( ized (ST p < 0.0

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SO, n = 7), swimming-trained sham (STS, n = 7) and swimming-trained ovariectomukey’s post hoc test was used. *p < 0.05 and **p < 0.01 vs. SS group; #p < 0.05 and ##

owever, the SO group showed an increase in the ANG II-inducedasoconstriction at all, but not only in the first concentration whenompared with the SS (p < 0.05), STS (p < 0.05) and STO groupsp < 0.05) (Fig. 4). These results indicate that chronic swimmingraining was able to prevent the OVX-induced increase in vaso-onstriction in the coronary arterial bed.

. Discussion

Menopause increases the incidence of cardiovascular andetabolic diseases because of the decrease of 17-�-estradiol lev-

ls [54]. In parallel, hormone replacement therapy with estrogen isommonly adopted at this stage of a woman’s life. However, clinicaltudies, such as the Women’s Health Initiative (WHI) and the Heartnd Estrogen/progestin Replacement Study, have reported someontroversial findings regarding the protective effects of hormoneeplacement treatment (HRT) with estrogen on the cardiovascu-ar system [44,50]. It was demonstrated clinically that HRT doesot provide protection against myocardial infarction and CVD [26],lthough other studies showed beneficial effects [24,29,32]. There-ore, the effects of estrogen HRT on the cardiovascular systemuring menopause remain inconclusive. On the other hand, physi-al training promotes a series of physiological adaptations. One ofhe most important adaptations is a decrease in blood pressure orlood pressure control inside the ideal ranges for blood perfusion.hus, this study demonstrated that in ovariectomized rats (whichs an experimental model of menopause) the chronic swimmingraining caused decreases in CPP as well as in ANG II-induced vaso-onstriction in the coronary bed. Moreover, it was demonstratedhat 8 weeks of swimming training can prevent the accumulationf fat in ovariectomized rats.

With respect to the baseline CPP, previous studies have shownhat the OVX rats have reduced CPP without alterations in the

HR [35,47]. A possible explanation of this response could be the

odulation of the intracellular calcium (Ca2+) concentration bystrogen, since studies has indicated that this hormone inhibits thea2+ influx [16,52], may depress sarcoplasmatic reticulum calcium

TO, n = 7) groups. Data are expressed as the mean ± SEM. A one-way ANOVA with1 vs. SO group and +p < 0.05 vs. STS group.

release [22] or alters the Ca2+ conductance by sarcolema [12,41].Furthermore, direct whole-cell and single-channel patch-clampfindings demonstrated that estrogen stimulates the activity ofthe large-conductance, calcium- and voltage-activated potassiumchannel (BKCa) in coronary myocytes resulting in hyperpolariza-tion and increasing in the coronary blood flow [56]. On the otherhand, many studies have indicated a synergistic effect of estrogenand sympathetic activity on increased vascular tonus due to theinhibition of norepinephrine uptake [21]. An increase in reactivityto norepinephrine was reported in oophorectomized [42] and pre-puberal rats [9] treated with estrogen. However, the basis for thehigher baseline values of CPP in intact sham rats and whether thiselevation can exert a cardioprotective role remains unclear.

Nevertheless, consistent with our hypothesis, physical trainingdecreased the ANG II-induced vasoconstriction in ovariectomizedrats to similar levels of trained or sedentary rats with normal estro-gen levels. The vasoactive response to ANG II depends directly onthe receptor that it binds to, with AT2 or AT1 promoting vasodi-lation or vasoconstriction, respectively. Estrogen has been shownto decrease the expression of the AT1 receptor in various organs[14,37,53]. Conversely, Baiardi et al. have shown that estrogencauses an upregulation of both receptors in the kidneys of femalerats [4]. Moreover, the treatment of ovariectomized rats with estro-gen decreased the constriction induced by ANG II in aortic rings[6,53].

Physical exercise attenuates ANG II-induced vasoconstrictionby modulating the expression of the AT1 and AT2 receptors. ANGII binding to the AT1 receptor can activate gp91phox (Nox2), anenzyme subunit that generates reactive oxygen species (ROS),which decreases the bioavailability of nitric oxide (NO) [1,45]. In themammary artery of patients with coronary arterial disease, phys-ical exercise promoted an increase in AT2 mRNA and a decreasein AT1 mRNA and protein, gp91phox mRNA, Nox4 mRNA (another

homologue of gp91phox present in endothelial and vascular smoothmuscle cells) and p22phox33 mRNA [1]. These molecular changes arefollowed by reduced ROS production, which results in the atten-uation of the maximum vasoconstrictor response to ANG II [27].

P.W. Endlich et al. / Peptides 47 (2013) 29–35 33

Fig. 3. Effects swimming training on (A) intrinsic heart rate and (B) baseline coro-nary perfusion pressure in sedentary sham (SS, n = 7), sedentary ovariectomized (SO,n = 7), swimming-trained sham (STS, n = 7) and swimming-trained ovariectomized(T

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Fig. 4. Effects of swimming training on coronary vascular reactivity toANG II. Concentration–response curves to growing concentrations of ANG II(0.001–1000 ng) in sedentary sham (SS, n = 7), sedentary ovariectomized (SO, n = 7),swimming-trained sham (STS, n = 7) and swimming-trained ovariectomized (STO,

view, physical exercise is a non-pharmacological treatment, is inex-

STO, n = 7) groups. Data are expressed as the mean ± SEM. A one-way ANOVA withukey’s post hoc test was used. *p < 0.05 vs. SS group and *p < 0.01 vs. SS group.

oreover, physical exercise decreases the expression of ACE andT1 receptor in the heart [58] and plasma ANG II levels [60], changes

hat are associated with lower cardiac fibrosis [58] and a decreasen systemic blood pressure [60], respectively.

In addition to the vascular mechanism, adiposity is anothermportant factor that can enhance the risk of CVD in the post-

enopausal period. During the training protocol, the SO groupxhibited a significant increase in BW. A previous study analyzedhe possible causes involved in the fat gain caused by E2 deficiency,he authors observed that after OVX, the animals exhibited hyper-hagic behavior and reduced locomotor activity and were morerone to accumulating fat because of these changes in behavior57]. In addition, lipoprotein metabolism was altered (the rate ofipolysis was decreased and the activity of lipoprotein lipase in adi-ose tissue was augmented) in post-menopausal women [17]. Inice, estradiol supplementation also protected against adipocyte

ypertrophy and adipose tissue oxidative stress and inflamma-ion [51]. The fact that central fat accumulation is a consequencef estrogen deficiency is also supported by studies of aromataseene knockout (ArKO) mice (who cannot synthesize endogenousstrogens). Female ArKO mice exhibit obesity, characterized by

arked increases in the gonadal and intra-renal fat pads, as early

s 3 months of age [34]. Moreover, previous data from our labora-ory demonstrated that swimming training promotes an increase

n = 7) groups. Data are expressed as the mean ± SEM. A two-way ANOVA withTukey’s post hoc test was used. *p < 0.01 vs. SS group; #p < 0.01 vs. STO group and+p < 0.05 vs. STS group.

in plasmatic atrial natriuretic peptide (ANP) levels, which didnot occur by the practice of chronic running training [15]. Thus,according to the well-established lipolytic effect of the ANP in theadipocyte, we can speculate that this may be one of the mechanismsrelated to the decrease in the fat content in swimming-trained rats[38].

The increase in fat tissue because of E2 deficiency can be relatedto higher response to angiotensin II in coronary bed of ovariec-tomized rats when compared to other groups. The adipose tissueproduces angiotensinogen, which corresponds to approximately30% of the circulating level in rodents, also plays a role in the wholebody [28]. Thereafter, adipose tissue also expresses renin and ACE,which results in increased production of Ang II [28]. Moreover, in E2deficiency condition occurs the increase in AT1 receptor expressionin various organs [14,37], stimulating vascular smooth muscle con-traction [7]. Thus, the efficiency of physical training to preventingthese effects in the condition of E2 deficiency could be associatedwith the mechanisms reported above. Likewise, our results showedlower visceral fat pad weight in ovariectomized rats trained byswimming. Therefore, ST may protect against body weight gainand, consequently, the risk to the development of cardiovascularand metabolic diseases.

5. Conclusion

In summary, swimming training in OVX rats results in a reduc-tion of weight gain compared to the weight levels observed insedentary OVX animals. These results indicate that swimmingtraining may bring about important changes in body compositionin OVX animals. Moreover, this study supports the hypothesis thatphysical training decreases ANG II-induced vasoconstriction, oneof the most important components of the RAS, which has its activ-ity augmented with estrogen deficiency. From a practical point of

pensive and shows insignificant negative effects on the body. Thecurrent study and studies of a similar nature can help to elucidatethe role of physical exercise and its effectiveness as a prophylactic

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easure in the development of cardiovascular diseases afterenopause and thus, generating important information that may

ontribute to practical measures for improving quality of life inomen.

onflict of interest

None declared.

cknowledgements

The authors thank Dr. F. Souza and Dr. M. Borsoi from Universityospital-HUCAM/UFES for plasma biochemical analysis. This workas supported by Conselho Nacional de Desenvolvimento Cien-

ifico e Tecnológico-Casadinho, Coordenac ão de Aperfeic oamentoe Pessoal de Nível Superior, Fundac ão de Amparo à Pesquisa dospírito Santo and Fundo de Apoio à Ciência e Tecnologia do Municí-io de Vitória.

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