Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ.

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.

Resistance training and caloric restriction prevent systolic blood pressure rise by improving the nitric oxide effect on smooth muscle and morphological changes in the aorta of ovariectomized rats.

In this study, we investigated the effects of resistance training (RT), caloric restriction (CR), and the association of both interventions in aortic vascular reactivity and morphological alterations, matrix metalloproteinase-2 (MMP-2) activity, insulin resistance and systolic blood pressure (SBP) in ovariectomized rats. Fifty female Holtzman rats were subjected to ovariectomy and Sham surgery and distributed into the following groups: Sham-sedentary, ovariectomized-sedentary, ovariectomized-resistance training, ovariectomized-caloric restriction, and ovariectomized-resistance training and caloric restriction groups. RT and 30% CR protocols were performed for 13 weeks. Analyses were conducted to evaluate the following: acetylcholine and sodium nitroprusside-induced relaxation of aortic rings, MMP-2 activity, insulin tolerance test, highlighting of the aorta wall cross-sectional area by hematoxylin-eosin stain, aorta vessel remodeling and SBP. We observed that ovariectomy decreased the potency of dependent and independent endothelium relaxation and MMP-2 activity, prevented insulin resistance, promoted aorta vessel remodeling in the cross-sectional area, and promoted the media-to-lumen ratio, the collagen content, and the alteration of the structure and elastic fibers of the vessel. The effects of the ovariectomy could contribute to SBP increases. However, the association of exercise and diet improved the relaxation potency in dependent and independent endothelium relaxation, elevated MMP-2 activity, ameliorate insulin sensitivity, increased the aorta cross-sectional area and media-to-lumen ratio, decreased collagen content and promoted histological parameters of the aorta vessel wall, preventing the increase of SBP. CONCLUSION: Our study revealed that the RT and CR separately, and even associatively, improved vascular function, activated MMP-2, and produced a beneficial hypertrophic remodeling, preventing the elevation of SBP in ovariectomized rats.

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

BACKGROUND:: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). OBJECTIVE:: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. METHODS:: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. RESULTS:: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. CONCLUSION:: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats. FUNDAMENTOS:: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). OBJETIVO:: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. MÉTODOS:: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). RESULTADOS:: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. CONCLUSÃO:: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.

Bone mineral density is reduced by telmisartan in male spontaneously hypertensive rats.

BACKGROUND: Telmisartan, an angiotensin AT1 receptor blocker, and treadmill running were compared for their effects on bone mineral density (BMD) and biomechanical properties of male spontaneously hypertensive rats (SHR). It was hypothesized that running (18m/min/60min/d) and telmisartan (5mg/kg/d) would have a positive effect on bone parameters. METHODS: Three-month-old male SHRs were divided into three groups: sedentary (S), telmisartan (T), and exercise (E). At the end of an 8-week protocol, femur and lumbar vertebrae were analyzed by dual-energy X-ray absorptiometry (DXA) for bone mineral density and by the three-point bending test for biomechanical properties. Blood pressure in all groups was measured by a tail-cuff manometer. RESULTS: Telmisartan and treadmill running reduced blood pressure when compared to the sedentary group; however, telmisartan did not improve bone characteristics. Instead, it reduced BMD of femur total and lumbar vertebrae and worsened bone biomechanic properties. Treadmill running maintained bone characteristics and hence was effective in maintaining bone health. CONCLUSION: Results showed that telmisartan negatively affected bones suggesting that caution should be taken in possible therapeutic applications for protecting bone health in hypertensive conditions. More studies are necessary to clarify the mechanisms through which telmisartan favors bone loss in this model.

Bone metabolism in obese rats programmed by early weaning.

OBJECTIVE: Obesity and osteoporosis seem to have a common pathogenesis, especially because bone and adipose tissue have common origins. Since early weaning (EW) decreases adipogenesis and osteogenesis in neonate, further programming for obesity and hyperleptinemia, we hypothesized that these changes in adipogenesis could affect bone metabolism. MATERIALS/METHODS: Lactating rats were separated into 3 groups: control - dams whose pups ate milk throughout lactation; mechanical EW (MEW) - dams were involved with a bandage interrupting suckling in the last 3days of lactation; pharmacological EW (PEW) - dams were bromocriptine-treated (0.5mg/twice a day via intraperitoneal injection) 3days before weaning. The adult offspring was subjected to dual-energy X-ray absorptiometry and bone tissue was also evaluated by computed tomography, microcomputed tomography and biomechanical tests, beyond serum analyses. RESULTS: MEW and PEW presented higher total bone mineral density (BMD), total bone mineral content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both groups also presented increase of these parameters and higher femur BMD and fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral body radiodensity, trabecular number, stiffness and break load; lower trabecular separation, maximal deformation and break deformation, and also hyperleptinemia and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was lower for both groups. CONCLUSIONS: Since both models program for obesity and increased bone mass, and leptin increases plasma vitamin D levels, probably leptin is the link between obesity and higher bone mass.

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats / Tratamento com Resveratrol Normaliza a Função Endotelial e a Pressão Arterial em Ratas Ovariectomizadas

Abstract Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

Resumo Fundamentos: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Objetivo: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. Métodos: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). Resultados: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. Conclusão: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.

Estudo do comportamento cortisol, gh e insulina apos uma sessao de exercicio resistido agudo / Study of the behavior of cortisol, gh and insulin after a session of acute resisted exercise / Estudio del comportamiento de cortisol, gh e insulina despues de uma sesion de ejercicio resistido agudo

INTRODUÇÃO: Muitos trabalhos têm estudado o comportamento hormonal nos exercício resistido, entretanto poucos relacionam os hormônios cortisol, GH e insulina. OBJETIVO: Estudar os ajustes das concentrações plasmáticas dos hormônios cortisol, GH e insulina em exercícios resistidos de mesma intensidade com relação à massas musculares distintas. MÉTODOS: Dez voluntários, com 20,3 ± 4,2 anos, 74,1 ± 10,2 kg de peso, 177,2 ± 4,6 cm de estatura e 23,8 ± 3,2 kg/m2 de IMC, realizaram uma sessão de leg press (LP) e supino reto (SR) com quatro séries com 10 repetições a 70% 1 RM com três minutos de intervalo. Foram coletadas amostras de sangue para dosagem das concentrações plasmáticas de cortisol, GH e insulina em repouso (Pré) e em 0' (Rec. 0'), 30' (Rec. 30') e 90' (Rec. 90') de recuperação. RESULTADOS: As concentrações plasmáticas de cortisol foram significativamente reduzidas ao final da recuperação em LP (2,20±0,37 ng/dl para 1,33±0,38ng/dl) em relação à pré-dosagem. As concentrações de GH e insulina elevaram-se significativamente durante a recuperação. GH em LP foi significativamente maior em Rec. 0' (2,75±3,29 ng/ml para 9,60±5,32 ng/dl) do que em pré. A insulina elevou-se significativamente em Rec. 30' em LP (14,70±7,92 ulU/ml para 21,66 ± 8,61 ulU/ml) e em SR (6,17 ± 2,99 ulU/ml para 19,70 ± 13,8 ulU/ml) em relação à pré. As concentrações plasmáticas de insulina pré em LP foram significativamente superiores a SR (14,70 ulU/ml e 6,17 ± 2,99 ulU/ml). CONCLUSÃO: O exercício resistido promoveu diferentes ajustes nas concentrações hormonais de cortisol, GH e insulina durante o período de recuperação. .

INTRODUCTION: Many works have studied the hormonal behavior in resistance exercise, however, few relate the cortisol, GH and insulin hormones. OBJECTIVE: To study the adjustments of plasma concentrations of the cortisol, GH and insulin hormones in resisted exercises of the same relative intensity with different muscle musses. METHODS: Ten volunteers, aged 20.3 ± 4.2 years, weight 74.1 ± 10.2 Kg, 177.2 ± 4.6 cm of stature and 23.8 ± 3.2 Kg/m2 of BMI, underwent a session of leg press (LP) and bench press (BP) with four sets of 10 repetitions at 70% 1 RM with three minutes apart. We collected blood samples to measure plasma concentrations of cortisol, GH and insulin at rest (Pre) and 0' (Rec. 0'), 30' (Rec. 30') and 90' (Rec. 90') of recovery. RESULTS: Plasma concentrations of cortisol decreased significantly at the end of the recovery in LP (2.20 ± 0.37 ng/dl to 1.33 ± 0.38 ng/dl) compared to pre. The GH and insulin concentrations significantly increased during recovery. GH was significantly higher in LP Rec. 0' (2.75 ± 3.29 ng/ml to 9.60 ± 5.32 ng/dl) than in pre. Insulin was significantly elevated in Rec. 30' in LP (14.70 ± 7.92 ulU/ml to 21.66 ± 8.61 ulU/ml) and BP (6.17 ± 2.99 ulU/ml to 19.70 ± 13.8 ulU/ml) for pre. The plasma insulin concentrations pre PL were significantly higher in the BP (14.70 ulU/ml and 6.17 ± 2.99 ulU/ml). CONCLUSION: Resisted exercise promoted different adjustments in hormone concentrations of cortisol, GH and insulin during the recovery period. .

INTRODUCCIÓN: Muchos trabajos han estudiado el comportamiento hormonal en el ejercicio de resistencia, sin embargo, pocos se refieren el cortisol, GH y las hormonas insulina. OBJETIVO: Estudiar los ajustes de las concentraciones plasmáticas de las hormonas cortisol, GH e insulina en ejercicios resistidos, de igual intensidad, en relación con las masas musculares diferentes. MÉTODOS: Diez voluntarios, con 20,3 ± 4,2 años, 74,1 ± 10,2 kg de peso, 177,2 ± 4,6 cm de estatura y 23,8 ± 3,2 kg/m2 de IMC, realizaron una sesión de leg press (LP) y supino recto (SR) con cuatro series, de 10 repeticiones a 70% 1 RM, con tres minutos de intervalo. Se recolectaron muestras de sangre para dosificación de las concentraciones plasmáticas de cortisol, GH e insulina en reposo (Pré) y en 0' (Rec. 0'), 30' (Rec. 30') y 90' (Rec. 90') de recuperación. RESULTADOS: Las concentraciones plasmáticas de cortisol se redujeron significativamente al final de la recuperación en LP (2,20±0,37 ng/dl para 1,33±0,38ng/dl) en relación con la predosificación. Las concentraciones de GH e insulina aumentaron significativamente durante la recuperación. GH en LP fue significativamente mayor en Rec. 0' (2,75±3,29 ng/ml para 9,60±5,32 ng/dl) en comparación con la predosificación. La insulina se elevó significativamente en Rec. 30' en LP (14,70±7,92 ulU/ml para 21,66 ± 8,61 ulU/ml) y en SR (6,17 ± 2,99 ulU/ml para 19,70 ± 13,8 ulU/ml) en relación con la predosificación. Las concentraciones plasmáticas de insulina, predosificación, en LP fueron significativamente superiores a SR (14,70 ulU/ml y 6,17 ± 2,99 ulU/ml). CONCLUSIÓN: El ejercicio resistido causó diferentes ajustes en las concentraciones hormonales de cortisol, GH e insulina durante el período de recuperación. .