l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease.

Chronic kidney disease (CKD) patients present L-arginine (L-arg) deficiency and L-arg supplementation has been used as a treatment. In addition, sarcopenia is another common problem in CKD population, resistance training (RT) is one of the conservative strategies developed to prevent CKD progression, and however there are no evidences of a combination of these two strategies to treat CKD outcomes. The aim of this study was to evaluate the effects of oral L-arg supplementation combined with RT in an experimental model of CKD. Twenty-five Munich-Wistar male rats, 8-week-old were divided in 5 groups: Sham (sedentary control), Nx (CKD sedentary), Nx L-arg (CKD sedentary supplemented with 2% of L-arg), Nx RT (CKD exercised) Nx RT + L-arg (CKD exercised and supplemented with 2% of L-arg). CKD model was obtained by a subtotal 5/6 nephrectomy. RT was performed on a ladder climbing, three weekly sessions on non-consecutive days, with an intensity of 70% maximum carrying capacity. They were submitted to RT and/or L-arg supplementation for 10 weeks. There was a significant improvement in muscle strength, renal function, anti-inflammatory cytokines, arginase metabolism and renal fibrosis after RT. However, the combination of RT and L-arg impaired all the improvements promoted by RT alone. The L-arg supplementation alone did not impair renal fibrosis and renal function. In conclusion, RT improved inflammatory balance, muscle strength, renal function and consequently decreased renal fibrosis. Nevertheless, the association with L-arg supplementation prevented all these effects promoted by RT.

Resistance training downregulates macrophages infiltration in the kidney of 5/6 nephrectomized rats.

INTRODUCTION: Chronic kidney disease (CKD) is considered a significant world health problem with elevated mortality rates. Patients with CKD are restricted to mild physical activity, present chronic inflammatory state and loss of muscle strength. Currently, the influence of resistance exercise (RE) on the progression of renal disease has not being fully elucidated. PURPOSE: To evaluate the effects of RE on the progression of CKD in a remnant kidney model (5/6Nx) in rats. METHODS: Eight-week-old Wistar rats were submitted to 5/6 nephrectomy and were divided into four groups: Sham sedentary (Sham SD); Sham RE (Sham RE); 5/6Nx SD and 5/6Nx RE. The animals were trained for 8 weeks in a vertical climbing ladder for 3 days per week, on non-consecutive days. RESULTS: As expected, 5/6Nx SD group presented a markedly loss of renal function, increased plasma inflammatory cytokines and increased oxidative stress with a reduced activity of nitric oxide. The higher macrophage infiltration and fibrosis confirmed these conditions. RE attenuated systolic blood pressure and renal function decrease and also improved serum lipid parameters in 5/6 Nx animals. It was evident the increase of muscle strength and mass in the trained groups while the sedentary group showed reduced muscle weight and strength compared to Sham SD. CONCLUSIONS: RE implemented following 5/6Nx retard the progression of chronic kidney injury while simultaneously allowed the maintenance of skeletal muscle strength.

Treinamento de Força Moderado Atenua o Aumento da Pressão Arterial e Diminui o Número de Núcleos em Cardiomiócitos de Ratos Hipertensos / Moderate Resistance Training Attenuates the Increase in Blood Pressure and Decreases the Cardiomyocyte Nuclei Number in Hypertensive Rats

O treinamento de força (TF) é uma estratégia que diminui a pressão arterial (PA) em pacientes com hipertensão arterial (HA) estágio 1 e atenua a progressão da PA em ratos hipertensos (estágio 3). A influência do TF na remodelação cardíaca na HA não controlada ainda não está estabelecida. Objetivo: O objetivo deste estudo foi avaliar os efeitos a longo prazo do TF em intensidade moderada na remodelação cardíaca em ratos espontaneamente hipertensos (SHRs) sem tratamento. Métodos: Dez SHRs machos com HA estágio 3 (PA sistólica ≥ 180 mmHg) e cinco ratos Wistar-Kyoto (WKY) normotensos (PA sistólica < 120 mmHg) foram divididos em três grupos: sedentários normotensos (SED-WKY), sedentários hipertensos (SED-SHR) e hipertensos TF (TF-SHR). O TF foi realizado em uma escada vertical (3 dias / semana por 12 semanas, em dias não consecutivos) com 70% da carga máxima. A PA e a frequência cardíaca foram registradas. Ao final do protocolo, os animais foram sacrificados e tiveram o ventrículo esquerdo seccionado para análise histológica (hematoxilina e eosina e picrosirius red). Resultados: O TF não atenuou o ganho de peso absoluto e relativo do coração e do ventrículo esquerdo no grupo TF-SHR em comparação ao grupo SED-SHR. Não houve nenhuma diferença no volume nuclear nos cardiomiócitos e conteúdo de colágeno entre os grupos. No entanto, o TF diminuiu o número de núcleos nos cardiomiócitos e atenuou o aumento da PA sistólica no grupo TF-SHR em relação ao grupo SED-SHR. O Δ do duplo produto foi menor no grupo TF-SHR em comparação aos grupos SED-WKY e SED-SHR. Conclusões: Os dados obtidos demonstram que o TF não atenuou a hipertrofia cardíaca, mas reduziu a proliferação nuclear nos cardiomiócitos e a progressão da PA em SHR com HA severa.

Resistance training (RT) is a strategy that decreases blood pressure (BP) in patients with stage 1 hypertension and attenuates BP progression in hypertensive rats (stage 3). The influence of RT in cardiac remodeling in uncontrolled hypertension is not yet established. Objective: The aim of this study was to evaluate the long-term effects of RT in moderate intensity in cardiac remodeling in spontaneously hypertensive rats (SHRs) without treatment. Methods: Ten male SHRs with stage 3 hypertension (systolic BP ≥ 180 mmHg) and five normotensive Wistar-Kyoto (WKY) rats (systolic BP < 120 mmHg) were divided into three groups: sedentary normotensive (SED-WKY), sedentary hypertensive (SED-SHR), and RT hypertensive (RT-SHR). The RT was conducted in a vertical ladder (3 days/week for 12 weeks, on nonconsecutive days) at 70% of the maximum load. BP and heart rate were recorded. At the end of the protocol, the animals were euthanized and had their left ventricles sectioned for histological analysis (hematoxylin and eosin and picrosirius red). Results: RT did not attenuate the absolute and relative weight gains of the heart and left ventricle in the RT-SHR group compared with the sedentary group (SED-SHR). There was no difference in nuclear cardiomyocyte volume and collagen content between groups. However, RT decreased the number of nuclei in the cardiomyocytes and attenuated the increase in systolic BP in the RT-SHR when compared with the SED-SHR group. The Δ of the rate-pressure product was lower in the RT-SHR group compared with the groups SED-WKY and SED-SHR. Conclusions: The data obtained demonstrate that RT did not attenuate the cardiac hypertrophy, but reduced the nuclear proliferation in cardiomyocytes and the BP progression in SHRs with severe hypertension.

Cardiovascular and Renal Effects of Birdseed Associated with Aerobic Exercise in Rats.

INTRODUCTION: Phalaris canariensis L. (Pc), known as birdseed, is rich in tryptophan. The aqueous extract of Pc (AEPc) treatment reduced systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) via mechanisms mediated by the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Hypertension is a risk factor to cardiovascular and renal diseases. Considering that physical exercise improves hypertension and cardiovascular function, the aim of this study was to evaluate whether the benefits of exercise (Ex) would be enhanced by concomitant AEPc treatment (400 mg·kg·d p.o.). METHODS: Vascular reactivity was assessed in aorta rings from SHR treated with AEPc for 4 wk. Training intensity was based on maximal lactate steady state obtained during the 2-wk adaptation period in a treadmill running. Then exercised (60 min running, five times per week during 8 wk) or sedentary SHR were untreated or treated with AEPc during 8 wk. SBP was estimated by plethysmograph. Heart mass and body mass were used to obtain the index of cardiac hypertrophy. Glucose tolerance test was evaluated by oral glucose overload, and the mRNA expressions of indoleamine 2,3-dioxygenase, interleukin 1ß (IL-1ß), and IL-10 in the kidney were obtained by real time polymerase chain reaction. RESULTS: AEPc induced endothelial-mediated vascular relaxation. AEPc or Ex alone reduced SBP, the index of cardiac hypertrophy and ventricular fibrosis, improved glucose metabolism, and attenuated proteinuria and the renal expression of the proinflammatory IL-1ß with an overexpression in the anti-inflammatory IL-10. AEPc potentiated the benefits of the Ex on the cardiovascular system, metabolic parameters, and renal inflammation. CONCLUSION: Birdseed reduced cardiovascular risk related to hypertension and had positive effects when associated to physical exercise.

Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension / Treinamento de Força em Ratos Espontaneamente Hipertensos com Hipertensão Arterial Grave

Abstract Background: Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective: This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBP)ENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

Resumo Fundamentos: O treinamento de força (TF) tem sido recomendado como tratamento não farmacológico para hipertensão arterial moderada. Apesar do papel importante que a intensidade do exercício desempenha sobre a prescrição do treinamento, ainda não há nenhum dado avaliando os efeitos da intensidade do TF sobre a hipertensão arterial grave (HAG). Objetivo: Este estudo analisou os efeitos de dois protocolos do TF(subida em escada vertical), realizados com diferentes sobrecargas do peso máximo carregado (PMC), sobre a pressão arterial (PA) e a força muscular de ratos espontaneamente hipertensos (SHR) com HAG. Métodos: Quinze SHR machos (206 ± 10 mmHg de PA sistólica (PAS)) e cinco ratos Wistar Kyoto (WKY; 119 ± 10 mmHg de PAS) foram divididos em 4grupos:sedentários: (SED-WKY) e SHR (SED-SHR); treinados: TF1-SHR conforme o peso corporal (~40% do PMC); e TF2-SHR conforme o teste de PMC (~70% do PMC). Foram coletadas medidas de PAS e a frequência cardíaca (FC) semanalmente usando o método de pressão arterial caudal. A progressão da força muscular foi determinada a cada 15 dias. O TF consistiu de 3 sessões semanais em dias não consecutivos durante 12 semanas. Resultados: Os dois protocolos de TF preveniram o aumento da PAS(respectivamente, delta - 5 e -7 mmHg; p > 0, 05), enquanto que a PAS do grupo SED-SHR aumentou em 19 mmHg (p < 0, 05). Houve queda na FC apenas para o grupo TF1 (p < 0, 05). Foi observado um aumento mas significativo de força no grupo do protocolo TF2 (140%; p < 0, 05) em comparação com o TF1 (11%; p>0, 05). Conclusões: Nossos dados indicam que ambos os protocolos de TF foram efetivos na prevenção da elevação crônica da PAS na HAG. Além disso, sobrecargas maiores de TF induziram a um maior aumento de força muscular.

Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension.

BACKGROUND: Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). OBJECTIVE: This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. METHODS: Fifteen male SHR ENT#091;206 ± 10 mmHg of systolic BP (SBP)ENT#093; and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. RESULTS: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). CONCLUSIONS: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength.

Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.

Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg(-1)·day(-1)) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.